Islet Autoimmunity Identifies a Unique Pattern of Impaired Pancreatic Beta-Cell Function, Markedly Reduced Pancreatic Beta Cell Mass and Insulin Resistance in Clinically Diagnosed Type 2 Diabetes
Identifieur interne : 002538 ( Main/Exploration ); précédent : 002537; suivant : 002539Islet Autoimmunity Identifies a Unique Pattern of Impaired Pancreatic Beta-Cell Function, Markedly Reduced Pancreatic Beta Cell Mass and Insulin Resistance in Clinically Diagnosed Type 2 Diabetes
Auteurs : Angela Subauste [États-Unis] ; Roberto Gianani [États-Unis] ; Annette M. Chang [États-Unis] ; Cynthia Plunkett [États-Unis] ; Susan L. Pietropaolo [États-Unis] ; Ying-Jian Zhang [États-Unis] ; Emma Barinas-Mitchell [États-Unis] ; Lewis H. Kuller [États-Unis] ; Andrzej Galecki [États-Unis] ; Jeffrey B. Halter [États-Unis] ; Massimo Pietropaolo [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Allèles, Antigènes HLA-DR (génétique), Antigènes HLA-DR (immunologie), Auto-immunité, Autoanticorps (immunologie), Cellules à insuline (anatomopathologie), Cellules à insuline (immunologie), Cellules à insuline (métabolisme), Composition corporelle, Diabète de type 2 (génétique), Diabète de type 2 (immunologie), Diabète de type 2 (métabolisme), Donneurs de tissus, Femelle, Glycémie, Humains, Insuline (sécrétion), Insulinorésistance, Marqueurs biologiques, Mâle, Peptide C (métabolisme), Sujet âgé, Taille de la cellule.
- MESH :
- anatomopathologie : Cellules à insuline.
- génétique : Antigènes HLA-DR, Diabète de type 2.
- immunologie : Antigènes HLA-DR, Autoanticorps, Cellules à insuline, Diabète de type 2.
- métabolisme : Cellules à insuline, Diabète de type 2, Peptide C.
- sécrétion : Insuline.
- Adulte, Adulte d'âge moyen, Allèles, Auto-immunité, Composition corporelle, Donneurs de tissus, Femelle, Glycémie, Humains, Insulinorésistance, Marqueurs biologiques, Mâle, Sujet âgé, Taille de la cellule.
English descriptors
- KwdEn :
- Adult, Aged, Alleles, Autoantibodies (immunology), Autoimmunity, Biomarkers, Blood Glucose, Body Composition, C-Peptide (metabolism), Cell Size, Diabetes Mellitus, Type 2 (genetics), Diabetes Mellitus, Type 2 (immunology), Diabetes Mellitus, Type 2 (metabolism), Female, HLA-DR Antigens (genetics), HLA-DR Antigens (immunology), Humans, Insulin (secretion), Insulin Resistance, Insulin-Secreting Cells (immunology), Insulin-Secreting Cells (metabolism), Insulin-Secreting Cells (pathology), Male, Middle Aged, Tissue Donors.
- MESH :
- chemical , genetics : HLA-DR Antigens.
- chemical , immunology : Autoantibodies, HLA-DR Antigens.
- chemical , metabolism : C-Peptide.
- genetics : Diabetes Mellitus, Type 2.
- immunology : Diabetes Mellitus, Type 2, Insulin-Secreting Cells.
- metabolism : Diabetes Mellitus, Type 2, Insulin-Secreting Cells.
- pathology : Insulin-Secreting Cells.
- chemical , secretion : Insulin.
- Adult, Aged, Alleles, Autoimmunity, Biomarkers, Blood Glucose, Body Composition, Cell Size, Female, Humans, Insulin Resistance, Male, Middle Aged, Tissue Donors.
Abstract
There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with at least 5-year duration of clinically diagnosed T2DM were evaluated in this study. In those subjects we assessed acute insulin responses to arginine, a glucose clamp study, whole-body fat mass and fat-free mass. We have also analyzed the pancreatic pathology of 15 T2DM and 43 control cadaveric donors, using pancreatic tissue obtained from all the T2DM organ donors available from the nPOD network through December 31, 2013. The presence of islet Ab correlated with severely impaired β-cell function as demonstrated by remarkably low acute insulin response to arginine (AIR) when compared to that of the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients exhibited peripheral insulin resistance in a similar fashion. Pathology data from T2DM donors with Ab or the autoimmune diabetes associated DR3/DR4 allelic class II combination showed reduction in beta cell mass as well as presence of autoimmune-associated pattern A pathology in subjects with either islet autoantibodies or the DR3/DR4 genotype. In conclusion, we provide compelling evidence indicating that islet Ab positive long-term T2DM patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic β-cells. Deciphering the mechanisms underlying beta cell destruction in this subset of diabetic patients may lead to the development of novel immunologic therapies aimed at halting the disease progression in its early stage.
Url:
DOI: 10.1371/journal.pone.0106537
PubMed: 25226365
PubMed Central: 4165581
Affiliations:
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Le document en format XML
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Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Division of Endocrinology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Endocrinology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi</wicri:regionArea><placeName><region type="state">État du Mississippi</region></placeName></affiliation></author><author><name sortKey="Gianani, Roberto" sort="Gianani, Roberto" uniqKey="Gianani R" first="Roberto" last="Gianani">Roberto Gianani</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Chang, Annette M" sort="Chang, Annette M" uniqKey="Chang A" first="Annette M." last="Chang">Annette M. Chang</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Plunkett, Cynthia" sort="Plunkett, Cynthia" uniqKey="Plunkett C" first="Cynthia" last="Plunkett">Cynthia Plunkett</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Pietropaolo, Susan L" sort="Pietropaolo, Susan L" uniqKey="Pietropaolo S" first="Susan L." last="Pietropaolo">Susan L. Pietropaolo</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Zhang, Ying Jian" sort="Zhang, Ying Jian" uniqKey="Zhang Y" first="Ying-Jian" last="Zhang">Ying-Jian Zhang</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Barinas Mitchell, Emma" sort="Barinas Mitchell, Emma" uniqKey="Barinas Mitchell E" first="Emma" last="Barinas-Mitchell">Emma Barinas-Mitchell</name><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Kuller, Lewis H" sort="Kuller, Lewis H" uniqKey="Kuller L" first="Lewis H." last="Kuller">Lewis H. Kuller</name><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Galecki, Andrzej" sort="Galecki, Andrzej" uniqKey="Galecki A" first="Andrzej" last="Galecki">Andrzej Galecki</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Geriatrics Center and Institute of Gerontology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Geriatrics Center and Institute of Gerontology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Halter, Jeffrey B" sort="Halter, Jeffrey B" uniqKey="Halter J" first="Jeffrey B." last="Halter">Jeffrey B. Halter</name><affiliation wicri:level="2"><nlm:aff id="aff3"><addr-line>Geriatrics Center and Institute of Gerontology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Geriatrics Center and Institute of Gerontology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Pietropaolo, Massimo" sort="Pietropaolo, Massimo" uniqKey="Pietropaolo M" first="Massimo" last="Pietropaolo">Massimo Pietropaolo</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Brehm Center for Diabetes Research, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Alleles</term><term>Autoantibodies (immunology)</term><term>Autoimmunity</term><term>Biomarkers</term><term>Blood Glucose</term><term>Body Composition</term><term>C-Peptide (metabolism)</term><term>Cell Size</term><term>Diabetes Mellitus, Type 2 (genetics)</term><term>Diabetes Mellitus, Type 2 (immunology)</term><term>Diabetes Mellitus, Type 2 (metabolism)</term><term>Female</term><term>HLA-DR Antigens (genetics)</term><term>HLA-DR Antigens (immunology)</term><term>Humans</term><term>Insulin (secretion)</term><term>Insulin Resistance</term><term>Insulin-Secreting Cells (immunology)</term><term>Insulin-Secreting Cells (metabolism)</term><term>Insulin-Secreting Cells (pathology)</term><term>Male</term><term>Middle Aged</term><term>Tissue Donors</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Allèles</term><term>Antigènes HLA-DR (génétique)</term><term>Antigènes HLA-DR (immunologie)</term><term>Auto-immunité</term><term>Autoanticorps (immunologie)</term><term>Cellules à insuline (anatomopathologie)</term><term>Cellules à insuline (immunologie)</term><term>Cellules à insuline (métabolisme)</term><term>Composition corporelle</term><term>Diabète de type 2 (génétique)</term><term>Diabète de type 2 (immunologie)</term><term>Diabète de type 2 (métabolisme)</term><term>Donneurs de tissus</term><term>Femelle</term><term>Glycémie</term><term>Humains</term><term>Insuline (sécrétion)</term><term>Insulinorésistance</term><term>Marqueurs biologiques</term><term>Mâle</term><term>Peptide C (métabolisme)</term><term>Sujet âgé</term><term>Taille de la cellule</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>HLA-DR Antigens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Autoantibodies</term><term>HLA-DR Antigens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>C-Peptide</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Cellules à insuline</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Diabetes Mellitus, Type 2</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes HLA-DR</term><term>Diabète de type 2</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes HLA-DR</term><term>Autoanticorps</term><term>Cellules à insuline</term><term>Diabète de type 2</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Diabetes Mellitus, Type 2</term><term>Insulin-Secreting Cells</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Diabetes Mellitus, Type 2</term><term>Insulin-Secreting Cells</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules à insuline</term><term>Diabète de type 2</term><term>Peptide C</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Insulin-Secreting Cells</term></keywords><keywords scheme="MESH" type="chemical" qualifier="secretion" xml:lang="en"><term>Insulin</term></keywords><keywords scheme="MESH" qualifier="sécrétion" xml:lang="fr"><term>Insuline</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Alleles</term><term>Autoimmunity</term><term>Biomarkers</term><term>Blood Glucose</term><term>Body Composition</term><term>Cell Size</term><term>Female</term><term>Humans</term><term>Insulin Resistance</term><term>Male</term><term>Middle Aged</term><term>Tissue Donors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Allèles</term><term>Auto-immunité</term><term>Composition corporelle</term><term>Donneurs de tissus</term><term>Femelle</term><term>Glycémie</term><term>Humains</term><term>Insulinorésistance</term><term>Marqueurs biologiques</term><term>Mâle</term><term>Sujet âgé</term><term>Taille de la cellule</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with at least 5-year duration of clinically diagnosed T2DM were evaluated in this study. In those subjects we assessed acute insulin responses to arginine, a glucose clamp study, whole-body fat mass and fat-free mass. We have also analyzed the pancreatic pathology of 15 T2DM and 43 control cadaveric donors, using pancreatic tissue obtained from all the T2DM organ donors available from the nPOD network through December 31, 2013. The presence of islet Ab correlated with severely impaired β-cell function as demonstrated by remarkably low acute insulin response to arginine (AIR) when compared to that of the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients exhibited peripheral insulin resistance in a similar fashion. Pathology data from T2DM donors with Ab or the autoimmune diabetes associated DR3/DR4 allelic class II combination showed reduction in beta cell mass as well as presence of autoimmune-associated pattern A pathology in subjects with either islet autoantibodies or the DR3/DR4 genotype. In conclusion, we provide compelling evidence indicating that islet Ab positive long-term T2DM patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic β-cells. Deciphering the mechanisms underlying beta cell destruction in this subset of diabetic patients may lead to the development of novel immunologic therapies aimed at halting the disease progression in its early stage.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Polonsky, Ks" uniqKey="Polonsky K">KS Polonsky</name></author><author><name sortKey="Sturis, J" uniqKey="Sturis J">J Sturis</name></author><author><name sortKey="Bell, Gi" uniqKey="Bell G">GI Bell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ward, Wk" uniqKey="Ward W">WK Ward</name></author><author><name sortKey="Bolgiano, Dc" uniqKey="Bolgiano D">DC Bolgiano</name></author><author><name sortKey="Mcknight, B" uniqKey="Mcknight B">B McKnight</name></author><author><name sortKey="Halter, Jb" uniqKey="Halter J">JB Halter</name></author><author><name sortKey="Porte, D" uniqKey="Porte D">D 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Maddux</name></author><author><name sortKey="Grodsky, Gm" uniqKey="Grodsky G">GM Grodsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ceriello, A" uniqKey="Ceriello A">A Ceriello</name></author><author><name sortKey="Esposito, K" uniqKey="Esposito K">K Esposito</name></author><author><name sortKey="Piconi, L" uniqKey="Piconi L">L Piconi</name></author><author><name sortKey="Ihnat, Ma" uniqKey="Ihnat M">MA Ihnat</name></author><author><name sortKey="Thorpe, Je" uniqKey="Thorpe J">JE Thorpe</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Michigan</li><li>Pennsylvanie</li><li>Texas</li><li>État du Mississippi</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Michigan"><name sortKey="Subauste, Angela" sort="Subauste, Angela" uniqKey="Subauste A" first="Angela" last="Subauste">Angela Subauste</name></region><name sortKey="Barinas Mitchell, Emma" sort="Barinas Mitchell, Emma" uniqKey="Barinas Mitchell E" first="Emma" last="Barinas-Mitchell">Emma Barinas-Mitchell</name><name sortKey="Chang, Annette M" sort="Chang, Annette M" uniqKey="Chang A" first="Annette M." last="Chang">Annette M. Chang</name><name sortKey="Galecki, Andrzej" sort="Galecki, Andrzej" uniqKey="Galecki A" first="Andrzej" last="Galecki">Andrzej Galecki</name><name sortKey="Gianani, Roberto" sort="Gianani, Roberto" uniqKey="Gianani R" first="Roberto" last="Gianani">Roberto Gianani</name><name sortKey="Gianani, Roberto" sort="Gianani, Roberto" uniqKey="Gianani R" first="Roberto" last="Gianani">Roberto Gianani</name><name sortKey="Halter, Jeffrey B" sort="Halter, Jeffrey B" uniqKey="Halter J" first="Jeffrey B." last="Halter">Jeffrey B. Halter</name><name sortKey="Kuller, Lewis H" sort="Kuller, Lewis H" uniqKey="Kuller L" first="Lewis H." last="Kuller">Lewis H. Kuller</name><name sortKey="Pietropaolo, Massimo" sort="Pietropaolo, Massimo" uniqKey="Pietropaolo M" first="Massimo" last="Pietropaolo">Massimo Pietropaolo</name><name sortKey="Pietropaolo, Massimo" sort="Pietropaolo, Massimo" uniqKey="Pietropaolo M" first="Massimo" last="Pietropaolo">Massimo Pietropaolo</name><name sortKey="Pietropaolo, Susan L" sort="Pietropaolo, Susan L" uniqKey="Pietropaolo S" first="Susan L." last="Pietropaolo">Susan L. Pietropaolo</name><name sortKey="Pietropaolo, Susan L" sort="Pietropaolo, Susan L" uniqKey="Pietropaolo S" first="Susan L." last="Pietropaolo">Susan L. Pietropaolo</name><name sortKey="Plunkett, Cynthia" sort="Plunkett, Cynthia" uniqKey="Plunkett C" first="Cynthia" last="Plunkett">Cynthia Plunkett</name><name sortKey="Subauste, Angela" sort="Subauste, Angela" uniqKey="Subauste A" first="Angela" last="Subauste">Angela Subauste</name><name sortKey="Zhang, Ying Jian" sort="Zhang, Ying Jian" uniqKey="Zhang Y" first="Ying-Jian" last="Zhang">Ying-Jian Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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