AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy.
Identifieur interne : 000F06 ( Main/Exploration ); précédent : 000F05; suivant : 000F07AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy.
Auteurs : Bernice Lo [États-Unis] ; Kejian Zhang [États-Unis] ; Wei Lu [États-Unis] ; Lixin Zheng [États-Unis] ; Qian Zhang [États-Unis] ; Chrysi Kanellopoulou [États-Unis] ; Yu Zhang [États-Unis] ; Zhiduo Liu [États-Unis] ; Jill M. Fritz [États-Unis] ; Rebecca Marsh [États-Unis] ; Ammar Husami [États-Unis] ; Diane Kissell [États-Unis] ; Shannon Nortman [États-Unis] ; Vijaya Chaturvedi [États-Unis] ; Hilary Haines [États-Unis] ; Lisa R. Young [États-Unis] ; Jun Mo [États-Unis] ; Alexandra H. Filipovich [États-Unis] ; Jack J. Bleesing [États-Unis] ; Peter Mustillo [États-Unis] ; Michael Stephens [États-Unis] ; Cesar M. Rueda [États-Unis] ; Claire A. Chougnet [États-Unis] ; Kasper Hoebe [États-Unis] ; Joshua Mcelwee [États-Unis] ; Jason D. Hughes [États-Unis] ; Elif Karakoc-Aydiner [Turquie] ; Helen F. Matthews [États-Unis] ; Susan Price [États-Unis] ; Helen C. Su [États-Unis] ; V Koneti Rao [États-Unis] ; Michael J. Lenardo [États-Unis] ; Michael B. Jordan [États-Unis]Source :
- Science (New York, N.Y.) [ 1095-9203 ] ; 2015.
Descripteurs français
- KwdFr :
- Abatacept, Activation des lymphocytes, Adolescent, Antigène CTLA-4 (déficit), Antigène CTLA-4 (génétique), Cellules HEK293, Chloroquine (pharmacologie), Déficit immunitaire commun variable (métabolisme), Déficit immunitaire commun variable (traitement médicamenteux), Endosomes (métabolisme), Enfant, Facteurs de transcription Forkhead (analyse), Femelle, Humains, Immunoconjugués (usage thérapeutique), Jeune adulte, Lymphocytes T (), Lymphocytes T (immunologie), Lysosomes (métabolisme), Maladies auto-immunes (métabolisme), Maladies auto-immunes (traitement médicamenteux), Mâle, Pneumopathies interstitielles (métabolisme), Pneumopathies interstitielles (traitement médicamenteux), Protéines adaptatrices de la transduction du signal (génétique), Protéines adaptatrices de la transduction du signal (métabolisme), Protéolyse, Techniques de knock-down de gènes.
- MESH :
- analyse : Facteurs de transcription Forkhead.
- déficit : Antigène CTLA-4.
- génétique : Antigène CTLA-4, Protéines adaptatrices de la transduction du signal.
- immunologie : Lymphocytes T.
- métabolisme : Déficit immunitaire commun variable, Endosomes, Lysosomes, Maladies auto-immunes, Pneumopathies interstitielles, Protéines adaptatrices de la transduction du signal.
- pharmacologie : Chloroquine.
- traitement médicamenteux : Déficit immunitaire commun variable, Maladies auto-immunes, Pneumopathies interstitielles.
- usage thérapeutique : Immunoconjugués.
- Abatacept, Activation des lymphocytes, Adolescent, Cellules HEK293, Enfant, Femelle, Humains, Jeune adulte, Lymphocytes T, Mâle, Protéolyse, Techniques de knock-down de gènes.
English descriptors
- KwdEn :
- Abatacept, Adaptor Proteins, Signal Transducing (genetics), Adaptor Proteins, Signal Transducing (metabolism), Adolescent, Autoimmune Diseases (drug therapy), Autoimmune Diseases (metabolism), CTLA-4 Antigen (deficiency), CTLA-4 Antigen (genetics), Child, Chloroquine (pharmacology), Common Variable Immunodeficiency (drug therapy), Common Variable Immunodeficiency (metabolism), Endosomes (metabolism), Female, Forkhead Transcription Factors (analysis), Gene Knockdown Techniques, HEK293 Cells, Humans, Immunoconjugates (therapeutic use), Lung Diseases, Interstitial (drug therapy), Lung Diseases, Interstitial (metabolism), Lymphocyte Activation, Lysosomes (metabolism), Male, Proteolysis, T-Lymphocytes (drug effects), T-Lymphocytes (immunology), Young Adult.
- MESH :
- chemical , analysis : Forkhead Transcription Factors.
- chemical , deficiency : CTLA-4 Antigen.
- chemical , genetics : Adaptor Proteins, Signal Transducing, CTLA-4 Antigen.
- chemical , metabolism : Adaptor Proteins, Signal Transducing.
- chemical , pharmacology : Chloroquine.
- chemical , therapeutic use : Immunoconjugates.
- chemical : Abatacept.
- drug effects : T-Lymphocytes.
- drug therapy : Autoimmune Diseases, Common Variable Immunodeficiency, Lung Diseases, Interstitial.
- immunology : T-Lymphocytes.
- metabolism : Autoimmune Diseases, Common Variable Immunodeficiency, Endosomes, Lung Diseases, Interstitial, Lysosomes.
- Adolescent, Child, Female, Gene Knockdown Techniques, HEK293 Cells, Humans, Lymphocyte Activation, Male, Proteolysis, Young Adult.
Abstract
Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige-like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. The biological role of LRBA in immunologic disease is unknown. We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-immunoglobulin fusion drug. Clinical responses and homology of LRBA to proteins controlling intracellular trafficking led us to hypothesize that it regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or knockdown increased CTLA4 turnover, which resulted in reduced levels of CTLA4 protein in FoxP3(+) regulatory and activated conventional T cells. In LRBA-deficient cells, inhibition of lysosome degradation with chloroquine prevented CTLA4 loss. These findings elucidate a mechanism for CTLA4 trafficking and control of immune responses and suggest therapies for diseases involving the CTLA4 pathway.
DOI: 10.1126/science.aaa1663
PubMed: 26206937
Affiliations:
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NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. michael.jordan@cchmc.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 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NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 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NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name><affiliation wicri:level="2"><nlm:affiliation>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 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Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Liu, Zhiduo" sort="Liu, Zhiduo" uniqKey="Liu Z" first="Zhiduo" last="Liu">Zhiduo Liu</name><affiliation wicri:level="2"><nlm:affiliation>Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Fritz, Jill M" sort="Fritz, Jill M" uniqKey="Fritz J" first="Jill M" last="Fritz">Jill M. Fritz</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Marsh, Rebecca" sort="Marsh, Rebecca" uniqKey="Marsh R" first="Rebecca" last="Marsh">Rebecca Marsh</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Husami, Ammar" sort="Husami, Ammar" uniqKey="Husami A" first="Ammar" last="Husami">Ammar Husami</name><affiliation wicri:level="2"><nlm:affiliation>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Kissell, Diane" sort="Kissell, Diane" uniqKey="Kissell D" first="Diane" last="Kissell">Diane Kissell</name><affiliation wicri:level="2"><nlm:affiliation>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Nortman, Shannon" sort="Nortman, Shannon" uniqKey="Nortman S" first="Shannon" last="Nortman">Shannon Nortman</name><affiliation wicri:level="2"><nlm:affiliation>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Chaturvedi, Vijaya" sort="Chaturvedi, Vijaya" uniqKey="Chaturvedi V" first="Vijaya" last="Chaturvedi">Vijaya Chaturvedi</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Haines, Hilary" sort="Haines, Hilary" uniqKey="Haines H" first="Hilary" last="Haines">Hilary Haines</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL</wicri:regionArea><placeName><region type="state">Alabama</region></placeName></affiliation></author><author><name sortKey="Young, Lisa R" sort="Young, Lisa R" uniqKey="Young L" first="Lisa R" last="Young">Lisa R. Young</name><affiliation wicri:level="2"><nlm:affiliation>Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Mo, Jun" sort="Mo, Jun" uniqKey="Mo J" first="Jun" last="Mo">Jun Mo</name><affiliation wicri:level="2"><nlm:affiliation>Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Filipovich, Alexandra H" sort="Filipovich, Alexandra H" uniqKey="Filipovich A" first="Alexandra H" last="Filipovich">Alexandra H. Filipovich</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Bleesing, Jack J" sort="Bleesing, Jack J" uniqKey="Bleesing J" first="Jack J" last="Bleesing">Jack J. Bleesing</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Mustillo, Peter" sort="Mustillo, Peter" uniqKey="Mustillo P" first="Peter" last="Mustillo">Peter Mustillo</name><affiliation wicri:level="2"><nlm:affiliation>Section of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Stephens, Michael" sort="Stephens, Michael" uniqKey="Stephens M" first="Michael" last="Stephens">Michael Stephens</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Rueda, Cesar M" sort="Rueda, Cesar M" uniqKey="Rueda C" first="Cesar M" last="Rueda">Cesar M. Rueda</name><affiliation wicri:level="2"><nlm:affiliation>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Chougnet, Claire A" sort="Chougnet, Claire A" uniqKey="Chougnet C" first="Claire A" last="Chougnet">Claire A. Chougnet</name><affiliation wicri:level="2"><nlm:affiliation>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Hoebe, Kasper" sort="Hoebe, Kasper" uniqKey="Hoebe K" first="Kasper" last="Hoebe">Kasper Hoebe</name><affiliation wicri:level="2"><nlm:affiliation>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Mcelwee, Joshua" sort="Mcelwee, Joshua" uniqKey="Mcelwee J" first="Joshua" last="Mcelwee">Joshua Mcelwee</name><affiliation wicri:level="2"><nlm:affiliation>Merck Research Laboratories, Merck & Co, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Merck Research Laboratories, Merck & Co, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hughes, Jason D" sort="Hughes, Jason D" uniqKey="Hughes J" first="Jason D" last="Hughes">Jason D. Hughes</name><affiliation wicri:level="2"><nlm:affiliation>Merck Research Laboratories, Merck & Co, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Merck Research Laboratories, Merck & Co, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Karakoc Aydiner, Elif" sort="Karakoc Aydiner, Elif" uniqKey="Karakoc Aydiner E" first="Elif" last="Karakoc-Aydiner">Elif Karakoc-Aydiner</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL, USA. Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA, USA. Section of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH, USA. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA. Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA. Merck Research Laboratories, Merck & Co, Boston, MA, USA. Marmara University, Division of Pediatric Allergy and Immunology, Istanbul, Turkey.</nlm:affiliation><country xml:lang="fr">Turquie</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL, USA. Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA, USA. Section of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH, USA. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA. Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA. Merck Research Laboratories, Merck & Co, Boston, MA, USA. Marmara University, Division of Pediatric Allergy and Immunology, Istanbul</wicri:regionArea><wicri:noRegion>Istanbul</wicri:noRegion></affiliation></author><author><name sortKey="Matthews, Helen F" sort="Matthews, Helen F" uniqKey="Matthews H" first="Helen F" last="Matthews">Helen F. Matthews</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Price, Susan" sort="Price, Susan" uniqKey="Price S" first="Susan" last="Price">Susan Price</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Su, Helen C" sort="Su, Helen C" uniqKey="Su H" first="Helen C" last="Su">Helen C. Su</name><affiliation wicri:level="2"><nlm:affiliation>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Rao, V Koneti" sort="Rao, V Koneti" uniqKey="Rao V" first="V Koneti" last="Rao">V Koneti Rao</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Lenardo, Michael J" sort="Lenardo, Michael J" uniqKey="Lenardo M" first="Michael J" last="Lenardo">Michael J. Lenardo</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. michael.jordan@cchmc.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Jordan, Michael B" sort="Jordan, Michael B" uniqKey="Jordan M" first="Michael B" last="Jordan">Michael B. Jordan</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA. michael.jordan@cchmc.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26206937</idno><idno type="pmid">26206937</idno><idno type="doi">10.1126/science.aaa1663</idno><idno type="wicri:Area/PubMed/Corpus">000241</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000241</idno><idno type="wicri:Area/PubMed/Curation">000241</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000241</idno><idno type="wicri:Area/PubMed/Checkpoint">000261</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000261</idno><idno type="wicri:Area/Ncbi/Merge">000304</idno><idno type="wicri:Area/Ncbi/Curation">000304</idno><idno type="wicri:Area/Ncbi/Checkpoint">000304</idno><idno type="wicri:Area/Main/Merge">000F07</idno><idno type="wicri:Area/Main/Curation">000F06</idno><idno type="wicri:Area/Main/Exploration">000F06</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy.</title><author><name sortKey="Lo, Bernice" sort="Lo, Bernice" uniqKey="Lo B" first="Bernice" last="Lo">Bernice Lo</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. michael.jordan@cchmc.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Zhang, Kejian" sort="Zhang, Kejian" uniqKey="Zhang K" first="Kejian" last="Zhang">Kejian Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. michael.jordan@cchmc.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Lu, Wei" sort="Lu, Wei" uniqKey="Lu W" first="Wei" last="Lu">Wei Lu</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Zheng, Lixin" sort="Zheng, Lixin" uniqKey="Zheng L" first="Lixin" last="Zheng">Lixin Zheng</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name><affiliation wicri:level="2"><nlm:affiliation>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kanellopoulou, Chrysi" sort="Kanellopoulou, Chrysi" uniqKey="Kanellopoulou C" first="Chrysi" last="Kanellopoulou">Chrysi Kanellopoulou</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Zhang, Yu" sort="Zhang, Yu" uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name><affiliation wicri:level="2"><nlm:affiliation>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Liu, Zhiduo" sort="Liu, Zhiduo" uniqKey="Liu Z" first="Zhiduo" last="Liu">Zhiduo Liu</name><affiliation wicri:level="2"><nlm:affiliation>Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Fritz, Jill M" sort="Fritz, Jill M" uniqKey="Fritz J" first="Jill M" last="Fritz">Jill M. Fritz</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Marsh, Rebecca" sort="Marsh, Rebecca" uniqKey="Marsh R" first="Rebecca" last="Marsh">Rebecca Marsh</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Husami, Ammar" sort="Husami, Ammar" uniqKey="Husami A" first="Ammar" last="Husami">Ammar Husami</name><affiliation wicri:level="2"><nlm:affiliation>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Kissell, Diane" sort="Kissell, Diane" uniqKey="Kissell D" first="Diane" last="Kissell">Diane Kissell</name><affiliation wicri:level="2"><nlm:affiliation>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Nortman, Shannon" sort="Nortman, Shannon" uniqKey="Nortman S" first="Shannon" last="Nortman">Shannon Nortman</name><affiliation wicri:level="2"><nlm:affiliation>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Chaturvedi, Vijaya" sort="Chaturvedi, Vijaya" uniqKey="Chaturvedi V" first="Vijaya" last="Chaturvedi">Vijaya Chaturvedi</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Haines, Hilary" sort="Haines, Hilary" uniqKey="Haines H" first="Hilary" last="Haines">Hilary Haines</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL</wicri:regionArea><placeName><region type="state">Alabama</region></placeName></affiliation></author><author><name sortKey="Young, Lisa R" sort="Young, Lisa R" uniqKey="Young L" first="Lisa R" last="Young">Lisa R. Young</name><affiliation wicri:level="2"><nlm:affiliation>Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN</wicri:regionArea><placeName><region type="state">Tennessee</region></placeName></affiliation></author><author><name sortKey="Mo, Jun" sort="Mo, Jun" uniqKey="Mo J" first="Jun" last="Mo">Jun Mo</name><affiliation wicri:level="2"><nlm:affiliation>Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Filipovich, Alexandra H" sort="Filipovich, Alexandra H" uniqKey="Filipovich A" first="Alexandra H" last="Filipovich">Alexandra H. Filipovich</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Bleesing, Jack J" sort="Bleesing, Jack J" uniqKey="Bleesing J" first="Jack J" last="Bleesing">Jack J. Bleesing</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Mustillo, Peter" sort="Mustillo, Peter" uniqKey="Mustillo P" first="Peter" last="Mustillo">Peter Mustillo</name><affiliation wicri:level="2"><nlm:affiliation>Section of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Section of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Stephens, Michael" sort="Stephens, Michael" uniqKey="Stephens M" first="Michael" last="Stephens">Michael Stephens</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Rueda, Cesar M" sort="Rueda, Cesar M" uniqKey="Rueda C" first="Cesar M" last="Rueda">Cesar M. Rueda</name><affiliation wicri:level="2"><nlm:affiliation>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Chougnet, Claire A" sort="Chougnet, Claire A" uniqKey="Chougnet C" first="Claire A" last="Chougnet">Claire A. Chougnet</name><affiliation wicri:level="2"><nlm:affiliation>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Hoebe, Kasper" sort="Hoebe, Kasper" uniqKey="Hoebe K" first="Kasper" last="Hoebe">Kasper Hoebe</name><affiliation wicri:level="2"><nlm:affiliation>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Mcelwee, Joshua" sort="Mcelwee, Joshua" uniqKey="Mcelwee J" first="Joshua" last="Mcelwee">Joshua Mcelwee</name><affiliation wicri:level="2"><nlm:affiliation>Merck Research Laboratories, Merck & Co, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Merck Research Laboratories, Merck & Co, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hughes, Jason D" sort="Hughes, Jason D" uniqKey="Hughes J" first="Jason D" last="Hughes">Jason D. Hughes</name><affiliation wicri:level="2"><nlm:affiliation>Merck Research Laboratories, Merck & Co, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Merck Research Laboratories, Merck & Co, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Karakoc Aydiner, Elif" sort="Karakoc Aydiner, Elif" uniqKey="Karakoc Aydiner E" first="Elif" last="Karakoc-Aydiner">Elif Karakoc-Aydiner</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL, USA. Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA, USA. Section of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH, USA. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA. Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA. Merck Research Laboratories, Merck & Co, Boston, MA, USA. Marmara University, Division of Pediatric Allergy and Immunology, Istanbul, Turkey.</nlm:affiliation><country xml:lang="fr">Turquie</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, AL, USA. Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, and Division of Allergy, Pulmonary, and Critical Care, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. Departments of Pathology and Pediatrics, University of California, San Diego and Rady Children's Hospital, San Diego, CA, USA. Section of Allergy and Immunology, Nationwide Children's Hospital, Columbus, OH, USA. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA. Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA. Merck Research Laboratories, Merck & Co, Boston, MA, USA. Marmara University, Division of Pediatric Allergy and Immunology, Istanbul</wicri:regionArea><wicri:noRegion>Istanbul</wicri:noRegion></affiliation></author><author><name sortKey="Matthews, Helen F" sort="Matthews, Helen F" uniqKey="Matthews H" first="Helen F" last="Matthews">Helen F. Matthews</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Price, Susan" sort="Price, Susan" uniqKey="Price S" first="Susan" last="Price">Susan Price</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Su, Helen C" sort="Su, Helen C" uniqKey="Su H" first="Helen C" last="Su">Helen C. Su</name><affiliation wicri:level="2"><nlm:affiliation>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Human Immunological Diseases Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Rao, V Koneti" sort="Rao, V Koneti" uniqKey="Rao V" first="V Koneti" last="Rao">V Koneti Rao</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Lenardo, Michael J" sort="Lenardo, Michael J" uniqKey="Lenardo M" first="Michael J" last="Lenardo">Michael J. Lenardo</name><affiliation wicri:level="2"><nlm:affiliation>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. michael.jordan@cchmc.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular Development of the Immune System Section and Clinical and Molecular Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. NIAID Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Jordan, Michael B" sort="Jordan, Michael B" uniqKey="Jordan M" first="Michael B" last="Jordan">Michael B. Jordan</name><affiliation wicri:level="2"><nlm:affiliation>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH, USA. michael.jordan@cchmc.org.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center/ University of Cincinnati, Cincinnati, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author></analytic><series><title level="j">Science (New York, N.Y.)</title><idno type="eISSN">1095-9203</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abatacept</term><term>Adaptor Proteins, Signal Transducing (genetics)</term><term>Adaptor Proteins, Signal Transducing (metabolism)</term><term>Adolescent</term><term>Autoimmune Diseases (drug therapy)</term><term>Autoimmune Diseases (metabolism)</term><term>CTLA-4 Antigen (deficiency)</term><term>CTLA-4 Antigen (genetics)</term><term>Child</term><term>Chloroquine (pharmacology)</term><term>Common Variable Immunodeficiency (drug therapy)</term><term>Common Variable Immunodeficiency (metabolism)</term><term>Endosomes (metabolism)</term><term>Female</term><term>Forkhead Transcription Factors (analysis)</term><term>Gene Knockdown Techniques</term><term>HEK293 Cells</term><term>Humans</term><term>Immunoconjugates (therapeutic use)</term><term>Lung Diseases, Interstitial (drug therapy)</term><term>Lung Diseases, Interstitial (metabolism)</term><term>Lymphocyte Activation</term><term>Lysosomes (metabolism)</term><term>Male</term><term>Proteolysis</term><term>T-Lymphocytes (drug effects)</term><term>T-Lymphocytes (immunology)</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Abatacept</term><term>Activation des lymphocytes</term><term>Adolescent</term><term>Antigène CTLA-4 (déficit)</term><term>Antigène CTLA-4 (génétique)</term><term>Cellules HEK293</term><term>Chloroquine (pharmacologie)</term><term>Déficit immunitaire commun variable (métabolisme)</term><term>Déficit immunitaire commun variable (traitement médicamenteux)</term><term>Endosomes (métabolisme)</term><term>Enfant</term><term>Facteurs de transcription Forkhead (analyse)</term><term>Femelle</term><term>Humains</term><term>Immunoconjugués (usage thérapeutique)</term><term>Jeune adulte</term><term>Lymphocytes T ()</term><term>Lymphocytes T (immunologie)</term><term>Lysosomes (métabolisme)</term><term>Maladies auto-immunes (métabolisme)</term><term>Maladies auto-immunes (traitement médicamenteux)</term><term>Mâle</term><term>Pneumopathies interstitielles (métabolisme)</term><term>Pneumopathies interstitielles (traitement médicamenteux)</term><term>Protéines adaptatrices de la transduction du signal (génétique)</term><term>Protéines adaptatrices de la transduction du signal (métabolisme)</term><term>Protéolyse</term><term>Techniques de knock-down de gènes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Forkhead Transcription Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>CTLA-4 Antigen</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term><term>CTLA-4 Antigen</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Immunoconjugates</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Abatacept</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Facteurs de transcription Forkhead</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Autoimmune Diseases</term><term>Common Variable Immunodeficiency</term><term>Lung Diseases, Interstitial</term></keywords><keywords scheme="MESH" qualifier="déficit" xml:lang="fr"><term>Antigène CTLA-4</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigène CTLA-4</term><term>Protéines adaptatrices de la transduction du signal</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphocytes T</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Autoimmune Diseases</term><term>Common Variable Immunodeficiency</term><term>Endosomes</term><term>Lung Diseases, Interstitial</term><term>Lysosomes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Déficit immunitaire commun variable</term><term>Endosomes</term><term>Lysosomes</term><term>Maladies auto-immunes</term><term>Pneumopathies interstitielles</term><term>Protéines adaptatrices de la transduction du signal</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Déficit immunitaire commun variable</term><term>Maladies auto-immunes</term><term>Pneumopathies interstitielles</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Immunoconjugués</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Child</term><term>Female</term><term>Gene Knockdown Techniques</term><term>HEK293 Cells</term><term>Humans</term><term>Lymphocyte Activation</term><term>Male</term><term>Proteolysis</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Abatacept</term><term>Activation des lymphocytes</term><term>Adolescent</term><term>Cellules HEK293</term><term>Enfant</term><term>Femelle</term><term>Humains</term><term>Jeune adulte</term><term>Lymphocytes T</term><term>Mâle</term><term>Protéolyse</term><term>Techniques de knock-down de gènes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige-like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. The biological role of LRBA in immunologic disease is unknown. We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-immunoglobulin fusion drug. Clinical responses and homology of LRBA to proteins controlling intracellular trafficking led us to hypothesize that it regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or knockdown increased CTLA4 turnover, which resulted in reduced levels of CTLA4 protein in FoxP3(+) regulatory and activated conventional T cells. In LRBA-deficient cells, inhibition of lysosome degradation with chloroquine prevented CTLA4 loss. These findings elucidate a mechanism for CTLA4 trafficking and control of immune responses and suggest therapies for diseases involving the CTLA4 pathway. </div></front></TEI><affiliations><list><country><li>Turquie</li><li>États-Unis</li></country><region><li>Alabama</li><li>Californie</li><li>Maryland</li><li>Massachusetts</li><li>Minnesota</li><li>Ohio</li><li>Tennessee</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Lo, Bernice" sort="Lo, Bernice" uniqKey="Lo B" first="Bernice" last="Lo">Bernice Lo</name></region><name sortKey="Bleesing, Jack J" sort="Bleesing, Jack J" uniqKey="Bleesing J" first="Jack J" last="Bleesing">Jack J. Bleesing</name><name sortKey="Chaturvedi, Vijaya" sort="Chaturvedi, Vijaya" uniqKey="Chaturvedi V" first="Vijaya" last="Chaturvedi">Vijaya Chaturvedi</name><name sortKey="Chougnet, Claire A" sort="Chougnet, Claire A" uniqKey="Chougnet C" first="Claire A" last="Chougnet">Claire A. Chougnet</name><name sortKey="Filipovich, Alexandra H" sort="Filipovich, Alexandra H" uniqKey="Filipovich A" first="Alexandra H" last="Filipovich">Alexandra H. Filipovich</name><name sortKey="Fritz, Jill M" sort="Fritz, Jill M" uniqKey="Fritz J" first="Jill M" last="Fritz">Jill M. Fritz</name><name sortKey="Haines, Hilary" sort="Haines, Hilary" uniqKey="Haines H" first="Hilary" last="Haines">Hilary Haines</name><name sortKey="Hoebe, Kasper" sort="Hoebe, Kasper" uniqKey="Hoebe K" first="Kasper" last="Hoebe">Kasper Hoebe</name><name sortKey="Hughes, Jason D" sort="Hughes, Jason D" uniqKey="Hughes J" first="Jason D" last="Hughes">Jason D. Hughes</name><name sortKey="Husami, Ammar" sort="Husami, Ammar" uniqKey="Husami A" first="Ammar" last="Husami">Ammar Husami</name><name sortKey="Jordan, Michael B" sort="Jordan, Michael B" uniqKey="Jordan M" first="Michael B" last="Jordan">Michael B. Jordan</name><name sortKey="Kanellopoulou, Chrysi" sort="Kanellopoulou, Chrysi" uniqKey="Kanellopoulou C" first="Chrysi" last="Kanellopoulou">Chrysi Kanellopoulou</name><name sortKey="Kissell, Diane" sort="Kissell, Diane" uniqKey="Kissell D" first="Diane" last="Kissell">Diane Kissell</name><name sortKey="Lenardo, Michael J" sort="Lenardo, Michael J" uniqKey="Lenardo M" first="Michael J" last="Lenardo">Michael J. Lenardo</name><name sortKey="Liu, Zhiduo" sort="Liu, Zhiduo" uniqKey="Liu Z" first="Zhiduo" last="Liu">Zhiduo Liu</name><name sortKey="Lu, Wei" sort="Lu, Wei" uniqKey="Lu W" first="Wei" last="Lu">Wei Lu</name><name sortKey="Marsh, Rebecca" sort="Marsh, Rebecca" uniqKey="Marsh R" first="Rebecca" last="Marsh">Rebecca Marsh</name><name sortKey="Matthews, Helen F" sort="Matthews, Helen F" uniqKey="Matthews H" first="Helen F" last="Matthews">Helen F. Matthews</name><name sortKey="Mcelwee, Joshua" sort="Mcelwee, Joshua" uniqKey="Mcelwee J" first="Joshua" last="Mcelwee">Joshua Mcelwee</name><name sortKey="Mo, Jun" sort="Mo, Jun" uniqKey="Mo J" first="Jun" last="Mo">Jun Mo</name><name sortKey="Mustillo, Peter" sort="Mustillo, Peter" uniqKey="Mustillo P" first="Peter" last="Mustillo">Peter Mustillo</name><name sortKey="Nortman, Shannon" sort="Nortman, Shannon" uniqKey="Nortman S" first="Shannon" last="Nortman">Shannon Nortman</name><name sortKey="Price, Susan" sort="Price, Susan" uniqKey="Price S" first="Susan" last="Price">Susan Price</name><name sortKey="Rao, V Koneti" sort="Rao, V Koneti" uniqKey="Rao V" first="V Koneti" last="Rao">V Koneti Rao</name><name sortKey="Rueda, Cesar M" sort="Rueda, Cesar M" uniqKey="Rueda C" first="Cesar M" last="Rueda">Cesar M. Rueda</name><name sortKey="Stephens, Michael" sort="Stephens, Michael" uniqKey="Stephens M" first="Michael" last="Stephens">Michael Stephens</name><name sortKey="Su, Helen C" sort="Su, Helen C" uniqKey="Su H" first="Helen C" last="Su">Helen C. Su</name><name sortKey="Young, Lisa R" sort="Young, Lisa R" uniqKey="Young L" first="Lisa R" last="Young">Lisa R. Young</name><name sortKey="Zhang, Kejian" sort="Zhang, Kejian" uniqKey="Zhang K" first="Kejian" last="Zhang">Kejian Zhang</name><name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name><name sortKey="Zhang, Yu" sort="Zhang, Yu" uniqKey="Zhang Y" first="Yu" last="Zhang">Yu Zhang</name><name sortKey="Zheng, Lixin" sort="Zheng, Lixin" uniqKey="Zheng L" first="Lixin" last="Zheng">Lixin Zheng</name></country><country name="Turquie"><noRegion><name sortKey="Karakoc Aydiner, Elif" sort="Karakoc Aydiner, Elif" uniqKey="Karakoc Aydiner E" first="Elif" last="Karakoc-Aydiner">Elif Karakoc-Aydiner</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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