Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome
Identifieur interne : 000F80 ( PascalFrancis/Corpus ); précédent : 000F79; suivant : 000F81Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome
Auteurs : Simon T. Cliffe ; Donald B. Bloch ; Santi Suryani ; Erik-Jan Kamsteeg ; Danielle T. Avery ; Umaimainthan Palendira ; Joseph A. Church ; Brynn K. Wainstein ; Antonino Trizzino ; Gerard Lefranc ; Carlo Akatcherian ; Andre Megarbane ; Christian Gilissen ; Despina Moshous ; Janine Reichenbach ; Siraj Misbah ; Uli Salzer ; Mario Abinun ; Peck Y. Ong ; Polina Stepensky ; Ezia Ruga ; John B. Ziegler ; Melanie Wong ; Stuart G. Tangye ; Robert Lindeman ; Michael F. Buckley ; Tony RoscioliSource :
- Journal of allergy and clinical immunology [ 0091-6749 ] ; 2012.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Background: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic venoocclusive disease. Objectives: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. Methods: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. Results: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels, Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell- dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. Conclusion: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population.
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NO : | PASCAL 12-0379589 INIST |
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ET : | Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome |
AU : | CLIFFE (Simon T.); BLOCH (Donald B.); SURYANI (Santi); KAMSTEEG (Erik-Jan); AVERY (Danielle T.); PALENDIRA (Umaimainthan); CHURCH (Joseph A.); WAINSTEIN (Brynn K.); TRIZZINO (Antonino); LEFRANC (Gerard); AKATCHERIAN (Carlo); MEGARBANE (Andre); GILISSEN (Christian); MOSHOUS (Despina); REICHENBACH (Janine); MISBAH (Siraj); SALZER (Uli); ABINUN (Mario); ONG (Peck Y.); STEPENSKY (Polina); RUGA (Ezia); ZIEGLER (John B.); WONG (Melanie); TANGYE (Stuart G.); LINDEMAN (Robert); BUCKLEY (Michael F.); ROSCIOLI (Tony) |
AF : | Department of Haematology and Genetics, Prince of Wales Hospital/Sydney/Australie (1 aut., 25 aut., 26 aut., 27 aut.); Centre for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston and Harvard Medical School/Boston/Etats-Unis (2 aut.); Immunology Program, Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales/Sydney/Australie (3 aut., 5 aut., 6 aut., 24 aut.); Department of Human Genetics, Radboud University Nijmegen Medical Centre/Nijmegen/Pays-Bas (4 aut., 13 aut.); Division of Clinical Immunology and Allergy, Childrens Hospital Los Angeles/Etats-Unis (7 aut., 19 aut.); Department of Immunology & Infectious Diseases. Sydney Children's Hospital/Australie (8 aut., 22 aut.); Pediatric Hematology Oncology, Ospedale dei Bambini "G. Di Cristina," ARNAS Civico/Palermo/Italie (9 aut.); Institute of Human Genetics, CNRS, UPR 1142, and Université Montpellier 2/Montpellier/France (10 aut.); Department of Pediatrics, Hospital Hôtel-Dieu de France, Saint Joseph University/Beirut/Liban (11 aut.); Medical Genetics Unit, Faculty of Medicine, Saint Joseph University/Beirut/Liban (12 aut.); Faculté de Médecine René Descartes, Université Paris Descartes, Site Necker, IFR94, Paris, and Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Unité d'Immunologie et d'Hématologie Pédiatriques/Paris/France (14 aut.); Division of Immunology/Haematology/BMT and the Children's Research Centre, University Children's Hospital Zurich, and the Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich/Suisse (15 aut.); Department of Clinical Immunology, Oxford Centre for Clinical Immunology, John Radcliffe Hospital/Oxford/Royaume-Uni (16 aut.); Centre of Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg/Allemagne (17 aut.); Department of Paediatric Immunology, Newcastle General Hospital/Australie (18 aut.); Pediatric Hematology-Oncology and BMT, Hadassah University Hospital./Jerusalem/Jordanie (20 aut.); Department of Pediatrics, University of Padova/Padua/Italie (21 aut.); Department of Allergy, Immunology and Infectious Diseases, the Children's Hospital, Westmead/Sydney/Australie (23 aut.); School of Women and Children's Health, Sydney Children's Hospital and the University of New South Wales/Sydney/Australie (27 aut.) |
DT : | Publication en série; Niveau analytique |
SO : | Journal of allergy and clinical immunology; ISSN 0091-6749; Coden JACIBY; Etats-Unis; Da. 2012; Vol. 130; No. 3; Pp. 735-742; Bibl. 29 ref. |
LA : | Anglais |
EA : | Background: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic venoocclusive disease. Objectives: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. Methods: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. Results: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels, Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell- dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. Conclusion: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population. |
CC : | 002A06; 002B07; 002B06D01 |
FD : | Maladie veinoocclusive; Immunodéficit; Immunoglobulinopénie; Symptomatologie; Cellule; Homme; Association; Lymphocyte B; Multiplication cellulaire; Immunologie; Immunopathologie |
ED : | Venoocclusive disease; Immune deficiency; Agammaglobulinemia; Symptomatology; Cell; Human; Association; B-Lymphocyte; Cell proliferation; Immunology; Immunopathology |
SD : | Enfermedad venooclusiva; Inmunodeficiencia; Inmunoglobulinopenia; Sintomatología; Célula; Hombre; Asociación; Linfocito B; Multiplicación celular; Inmunología; Inmunopatología |
LO : | INIST-2059.354000508389870230 |
ID : | 12-0379589 |
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Pascal:12-0379589Le document en format XML
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<author><name sortKey="Gilissen, Christian" sort="Gilissen, Christian" uniqKey="Gilissen C" first="Christian" last="Gilissen">Christian Gilissen</name>
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<author><name sortKey="Ong, Peck Y" sort="Ong, Peck Y" uniqKey="Ong P" first="Peck Y." last="Ong">Peck Y. Ong</name>
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<author><name sortKey="Stepensky, Polina" sort="Stepensky, Polina" uniqKey="Stepensky P" first="Polina" last="Stepensky">Polina Stepensky</name>
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<author><name sortKey="Ruga, Ezia" sort="Ruga, Ezia" uniqKey="Ruga E" first="Ezia" last="Ruga">Ezia Ruga</name>
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<author><name sortKey="Ziegler, John B" sort="Ziegler, John B" uniqKey="Ziegler J" first="John B." last="Ziegler">John B. Ziegler</name>
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<author><name sortKey="Wong, Melanie" sort="Wong, Melanie" uniqKey="Wong M" first="Melanie" last="Wong">Melanie Wong</name>
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<author><name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G." last="Tangye">Stuart G. Tangye</name>
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<author><name sortKey="Lindeman, Robert" sort="Lindeman, Robert" uniqKey="Lindeman R" first="Robert" last="Lindeman">Robert Lindeman</name>
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<author><name sortKey="Buckley, Michael F" sort="Buckley, Michael F" uniqKey="Buckley M" first="Michael F." last="Buckley">Michael F. Buckley</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Haematology and Genetics, Prince of Wales Hospital</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
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<author><name sortKey="Roscioli, Tony" sort="Roscioli, Tony" uniqKey="Roscioli T" first="Tony" last="Roscioli">Tony Roscioli</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Haematology and Genetics, Prince of Wales Hospital</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
<sZ>27 aut.</sZ>
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<affiliation><inist:fA14 i1="19"><s1>School of Women and Children's Health, Sydney Children's Hospital and the University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>27 aut.</sZ>
</inist:fA14>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome</title>
<author><name sortKey="Cliffe, Simon T" sort="Cliffe, Simon T" uniqKey="Cliffe S" first="Simon T." last="Cliffe">Simon T. Cliffe</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Haematology and Genetics, Prince of Wales Hospital</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
<sZ>27 aut.</sZ>
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<author><name sortKey="Bloch, Donald B" sort="Bloch, Donald B" uniqKey="Bloch D" first="Donald B." last="Bloch">Donald B. Bloch</name>
<affiliation><inist:fA14 i1="02"><s1>Centre for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston and Harvard Medical School</s1>
<s2>Boston</s2>
<s3>USA</s3>
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<author><name sortKey="Suryani, Santi" sort="Suryani, Santi" uniqKey="Suryani S" first="Santi" last="Suryani">Santi Suryani</name>
<affiliation><inist:fA14 i1="03"><s1>Immunology Program, Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>3 aut.</sZ>
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<sZ>24 aut.</sZ>
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<author><name sortKey="Kamsteeg, Erik Jan" sort="Kamsteeg, Erik Jan" uniqKey="Kamsteeg E" first="Erik-Jan" last="Kamsteeg">Erik-Jan Kamsteeg</name>
<affiliation><inist:fA14 i1="04"><s1>Department of Human Genetics, Radboud University Nijmegen Medical Centre</s1>
<s2>Nijmegen</s2>
<s3>NLD</s3>
<sZ>4 aut.</sZ>
<sZ>13 aut.</sZ>
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<author><name sortKey="Avery, Danielle T" sort="Avery, Danielle T" uniqKey="Avery D" first="Danielle T." last="Avery">Danielle T. Avery</name>
<affiliation><inist:fA14 i1="03"><s1>Immunology Program, Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales</s1>
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<author><name sortKey="Palendira, Umaimainthan" sort="Palendira, Umaimainthan" uniqKey="Palendira U" first="Umaimainthan" last="Palendira">Umaimainthan Palendira</name>
<affiliation><inist:fA14 i1="03"><s1>Immunology Program, Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>24 aut.</sZ>
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<author><name sortKey="Church, Joseph A" sort="Church, Joseph A" uniqKey="Church J" first="Joseph A." last="Church">Joseph A. Church</name>
<affiliation><inist:fA14 i1="05"><s1>Division of Clinical Immunology and Allergy, Childrens Hospital Los Angeles</s1>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
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<author><name sortKey="Wainstein, Brynn K" sort="Wainstein, Brynn K" uniqKey="Wainstein B" first="Brynn K." last="Wainstein">Brynn K. Wainstein</name>
<affiliation><inist:fA14 i1="06"><s1>Department of Immunology & Infectious Diseases. Sydney Children's Hospital</s1>
<s3>AUS</s3>
<sZ>8 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Trizzino, Antonino" sort="Trizzino, Antonino" uniqKey="Trizzino A" first="Antonino" last="Trizzino">Antonino Trizzino</name>
<affiliation><inist:fA14 i1="07"><s1>Pediatric Hematology Oncology, Ospedale dei Bambini "G. Di Cristina," ARNAS Civico</s1>
<s2>Palermo</s2>
<s3>ITA</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Lefranc, Gerard" sort="Lefranc, Gerard" uniqKey="Lefranc G" first="Gerard" last="Lefranc">Gerard Lefranc</name>
<affiliation><inist:fA14 i1="08"><s1>Institute of Human Genetics, CNRS, UPR 1142, and Université Montpellier 2</s1>
<s2>Montpellier</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Akatcherian, Carlo" sort="Akatcherian, Carlo" uniqKey="Akatcherian C" first="Carlo" last="Akatcherian">Carlo Akatcherian</name>
<affiliation><inist:fA14 i1="09"><s1>Department of Pediatrics, Hospital Hôtel-Dieu de France, Saint Joseph University</s1>
<s2>Beirut</s2>
<s3>LBN</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Megarbane, Andre" sort="Megarbane, Andre" uniqKey="Megarbane A" first="Andre" last="Megarbane">Andre Megarbane</name>
<affiliation><inist:fA14 i1="10"><s1>Medical Genetics Unit, Faculty of Medicine, Saint Joseph University</s1>
<s2>Beirut</s2>
<s3>LBN</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Gilissen, Christian" sort="Gilissen, Christian" uniqKey="Gilissen C" first="Christian" last="Gilissen">Christian Gilissen</name>
<affiliation><inist:fA14 i1="04"><s1>Department of Human Genetics, Radboud University Nijmegen Medical Centre</s1>
<s2>Nijmegen</s2>
<s3>NLD</s3>
<sZ>4 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Moshous, Despina" sort="Moshous, Despina" uniqKey="Moshous D" first="Despina" last="Moshous">Despina Moshous</name>
<affiliation><inist:fA14 i1="11"><s1>Faculté de Médecine René Descartes, Université Paris Descartes, Site Necker, IFR94, Paris, and Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Unité d'Immunologie et d'Hématologie Pédiatriques</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Reichenbach, Janine" sort="Reichenbach, Janine" uniqKey="Reichenbach J" first="Janine" last="Reichenbach">Janine Reichenbach</name>
<affiliation><inist:fA14 i1="12"><s1>Division of Immunology/Haematology/BMT and the Children's Research Centre, University Children's Hospital Zurich, and the Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich</s1>
<s3>CHE</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Misbah, Siraj" sort="Misbah, Siraj" uniqKey="Misbah S" first="Siraj" last="Misbah">Siraj Misbah</name>
<affiliation><inist:fA14 i1="13"><s1>Department of Clinical Immunology, Oxford Centre for Clinical Immunology, John Radcliffe Hospital</s1>
<s2>Oxford</s2>
<s3>GBR</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Salzer, Uli" sort="Salzer, Uli" uniqKey="Salzer U" first="Uli" last="Salzer">Uli Salzer</name>
<affiliation><inist:fA14 i1="14"><s1>Centre of Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg</s1>
<s3>DEU</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Abinun, Mario" sort="Abinun, Mario" uniqKey="Abinun M" first="Mario" last="Abinun">Mario Abinun</name>
<affiliation><inist:fA14 i1="15"><s1>Department of Paediatric Immunology, Newcastle General Hospital</s1>
<s3>AUS</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Ong, Peck Y" sort="Ong, Peck Y" uniqKey="Ong P" first="Peck Y." last="Ong">Peck Y. Ong</name>
<affiliation><inist:fA14 i1="05"><s1>Division of Clinical Immunology and Allergy, Childrens Hospital Los Angeles</s1>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Stepensky, Polina" sort="Stepensky, Polina" uniqKey="Stepensky P" first="Polina" last="Stepensky">Polina Stepensky</name>
<affiliation><inist:fA14 i1="16"><s1>Pediatric Hematology-Oncology and BMT, Hadassah University Hospital.</s1>
<s2>Jerusalem</s2>
<s3>JOR</s3>
<sZ>20 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Ruga, Ezia" sort="Ruga, Ezia" uniqKey="Ruga E" first="Ezia" last="Ruga">Ezia Ruga</name>
<affiliation><inist:fA14 i1="17"><s1>Department of Pediatrics, University of Padova</s1>
<s2>Padua</s2>
<s3>ITA</s3>
<sZ>21 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Ziegler, John B" sort="Ziegler, John B" uniqKey="Ziegler J" first="John B." last="Ziegler">John B. Ziegler</name>
<affiliation><inist:fA14 i1="06"><s1>Department of Immunology & Infectious Diseases. Sydney Children's Hospital</s1>
<s3>AUS</s3>
<sZ>8 aut.</sZ>
<sZ>22 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Wong, Melanie" sort="Wong, Melanie" uniqKey="Wong M" first="Melanie" last="Wong">Melanie Wong</name>
<affiliation><inist:fA14 i1="18"><s1>Department of Allergy, Immunology and Infectious Diseases, the Children's Hospital, Westmead</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>23 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G." last="Tangye">Stuart G. Tangye</name>
<affiliation><inist:fA14 i1="03"><s1>Immunology Program, Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>24 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Lindeman, Robert" sort="Lindeman, Robert" uniqKey="Lindeman R" first="Robert" last="Lindeman">Robert Lindeman</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Haematology and Genetics, Prince of Wales Hospital</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
<sZ>27 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Buckley, Michael F" sort="Buckley, Michael F" uniqKey="Buckley M" first="Michael F." last="Buckley">Michael F. Buckley</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Haematology and Genetics, Prince of Wales Hospital</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
<sZ>27 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Roscioli, Tony" sort="Roscioli, Tony" uniqKey="Roscioli T" first="Tony" last="Roscioli">Tony Roscioli</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Haematology and Genetics, Prince of Wales Hospital</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
<sZ>27 aut.</sZ>
</inist:fA14>
</affiliation>
<affiliation><inist:fA14 i1="19"><s1>School of Women and Children's Health, Sydney Children's Hospital and the University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>27 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of allergy and clinical immunology</title>
<title level="j" type="abbreviated">J. allergy clin. immunol.</title>
<idno type="ISSN">0091-6749</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
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<seriesStmt><title level="j" type="main">Journal of allergy and clinical immunology</title>
<title level="j" type="abbreviated">J. allergy clin. immunol.</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Agammaglobulinemia</term>
<term>Association</term>
<term>B-Lymphocyte</term>
<term>Cell</term>
<term>Cell proliferation</term>
<term>Human</term>
<term>Immune deficiency</term>
<term>Immunology</term>
<term>Immunopathology</term>
<term>Symptomatology</term>
<term>Venoocclusive disease</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Maladie veinoocclusive</term>
<term>Immunodéficit</term>
<term>Immunoglobulinopénie</term>
<term>Symptomatologie</term>
<term>Cellule</term>
<term>Homme</term>
<term>Association</term>
<term>Lymphocyte B</term>
<term>Multiplication cellulaire</term>
<term>Immunologie</term>
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<front><div type="abstract" xml:lang="en">Background: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic venoocclusive disease. Objectives: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. Methods: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. Results: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels, Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell- dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. Conclusion: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population.</div>
</front>
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<fA11 i1="01" i2="1"><s1>CLIFFE (Simon T.)</s1>
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<fA11 i1="02" i2="1"><s1>BLOCH (Donald B.)</s1>
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<fA11 i1="09" i2="1"><s1>TRIZZINO (Antonino)</s1>
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<fA11 i1="10" i2="1"><s1>LEFRANC (Gerard)</s1>
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<fA11 i1="16" i2="1"><s1>MISBAH (Siraj)</s1>
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<fA11 i1="17" i2="1"><s1>SALZER (Uli)</s1>
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<fA11 i1="18" i2="1"><s1>ABINUN (Mario)</s1>
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<fA11 i1="19" i2="1"><s1>ONG (Peck Y.)</s1>
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<fA11 i1="20" i2="1"><s1>STEPENSKY (Polina)</s1>
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<fA11 i1="21" i2="1"><s1>RUGA (Ezia)</s1>
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<fA11 i1="22" i2="1"><s1>ZIEGLER (John B.)</s1>
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<fA11 i1="23" i2="1"><s1>WONG (Melanie)</s1>
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<fA11 i1="24" i2="1"><s1>TANGYE (Stuart G.)</s1>
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<fA11 i1="25" i2="1"><s1>LINDEMAN (Robert)</s1>
</fA11>
<fA11 i1="26" i2="1"><s1>BUCKLEY (Michael F.)</s1>
</fA11>
<fA11 i1="27" i2="1"><s1>ROSCIOLI (Tony)</s1>
</fA11>
<fA14 i1="01"><s1>Department of Haematology and Genetics, Prince of Wales Hospital</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>25 aut.</sZ>
<sZ>26 aut.</sZ>
<sZ>27 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Centre for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston and Harvard Medical School</s1>
<s2>Boston</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Immunology Program, Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>24 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Department of Human Genetics, Radboud University Nijmegen Medical Centre</s1>
<s2>Nijmegen</s2>
<s3>NLD</s3>
<sZ>4 aut.</sZ>
<sZ>13 aut.</sZ>
</fA14>
<fA14 i1="05"><s1>Division of Clinical Immunology and Allergy, Childrens Hospital Los Angeles</s1>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>19 aut.</sZ>
</fA14>
<fA14 i1="06"><s1>Department of Immunology & Infectious Diseases. Sydney Children's Hospital</s1>
<s3>AUS</s3>
<sZ>8 aut.</sZ>
<sZ>22 aut.</sZ>
</fA14>
<fA14 i1="07"><s1>Pediatric Hematology Oncology, Ospedale dei Bambini "G. Di Cristina," ARNAS Civico</s1>
<s2>Palermo</s2>
<s3>ITA</s3>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="08"><s1>Institute of Human Genetics, CNRS, UPR 1142, and Université Montpellier 2</s1>
<s2>Montpellier</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="09"><s1>Department of Pediatrics, Hospital Hôtel-Dieu de France, Saint Joseph University</s1>
<s2>Beirut</s2>
<s3>LBN</s3>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="10"><s1>Medical Genetics Unit, Faculty of Medicine, Saint Joseph University</s1>
<s2>Beirut</s2>
<s3>LBN</s3>
<sZ>12 aut.</sZ>
</fA14>
<fA14 i1="11"><s1>Faculté de Médecine René Descartes, Université Paris Descartes, Site Necker, IFR94, Paris, and Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Unité d'Immunologie et d'Hématologie Pédiatriques</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>14 aut.</sZ>
</fA14>
<fA14 i1="12"><s1>Division of Immunology/Haematology/BMT and the Children's Research Centre, University Children's Hospital Zurich, and the Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich</s1>
<s3>CHE</s3>
<sZ>15 aut.</sZ>
</fA14>
<fA14 i1="13"><s1>Department of Clinical Immunology, Oxford Centre for Clinical Immunology, John Radcliffe Hospital</s1>
<s2>Oxford</s2>
<s3>GBR</s3>
<sZ>16 aut.</sZ>
</fA14>
<fA14 i1="14"><s1>Centre of Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg</s1>
<s3>DEU</s3>
<sZ>17 aut.</sZ>
</fA14>
<fA14 i1="15"><s1>Department of Paediatric Immunology, Newcastle General Hospital</s1>
<s3>AUS</s3>
<sZ>18 aut.</sZ>
</fA14>
<fA14 i1="16"><s1>Pediatric Hematology-Oncology and BMT, Hadassah University Hospital.</s1>
<s2>Jerusalem</s2>
<s3>JOR</s3>
<sZ>20 aut.</sZ>
</fA14>
<fA14 i1="17"><s1>Department of Pediatrics, University of Padova</s1>
<s2>Padua</s2>
<s3>ITA</s3>
<sZ>21 aut.</sZ>
</fA14>
<fA14 i1="18"><s1>Department of Allergy, Immunology and Infectious Diseases, the Children's Hospital, Westmead</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>23 aut.</sZ>
</fA14>
<fA14 i1="19"><s1>School of Women and Children's Health, Sydney Children's Hospital and the University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>27 aut.</sZ>
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<fC01 i1="01" l="ENG"><s0>Background: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic venoocclusive disease. Objectives: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. Methods: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. Results: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels, Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell- dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. Conclusion: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population.</s0>
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<fC03 i1="02" i2="X" l="ENG"><s0>Immune deficiency</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Inmunodeficiencia</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Immunoglobulinopénie</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Agammaglobulinemia</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Inmunoglobulinopenia</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Symptomatologie</s0>
<s5>09</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Symptomatology</s0>
<s5>09</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Sintomatología</s0>
<s5>09</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Cellule</s0>
<s5>10</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Cell</s0>
<s5>10</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Célula</s0>
<s5>10</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Homme</s0>
<s5>11</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Human</s0>
<s5>11</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Hombre</s0>
<s5>11</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Association</s0>
<s5>12</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Association</s0>
<s5>12</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Asociación</s0>
<s5>12</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Lymphocyte B</s0>
<s5>13</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>B-Lymphocyte</s0>
<s5>13</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Linfocito B</s0>
<s5>13</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Multiplication cellulaire</s0>
<s5>14</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Cell proliferation</s0>
<s5>14</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Multiplicación celular</s0>
<s5>14</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Immunologie</s0>
<s5>15</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Immunology</s0>
<s5>15</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Inmunología</s0>
<s5>15</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Immunopathologie</s0>
<s5>16</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Immunopathology</s0>
<s5>16</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Inmunopatología</s0>
<s5>16</s5>
</fC03>
<fN21><s1>296</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
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<server><NO>PASCAL 12-0379589 INIST</NO>
<ET>Clinical, molecular, and cellular immunologic findings in patients with SP110-associated veno-occlusive disease with immunodeficiency syndrome</ET>
<AU>CLIFFE (Simon T.); BLOCH (Donald B.); SURYANI (Santi); KAMSTEEG (Erik-Jan); AVERY (Danielle T.); PALENDIRA (Umaimainthan); CHURCH (Joseph A.); WAINSTEIN (Brynn K.); TRIZZINO (Antonino); LEFRANC (Gerard); AKATCHERIAN (Carlo); MEGARBANE (Andre); GILISSEN (Christian); MOSHOUS (Despina); REICHENBACH (Janine); MISBAH (Siraj); SALZER (Uli); ABINUN (Mario); ONG (Peck Y.); STEPENSKY (Polina); RUGA (Ezia); ZIEGLER (John B.); WONG (Melanie); TANGYE (Stuart G.); LINDEMAN (Robert); BUCKLEY (Michael F.); ROSCIOLI (Tony)</AU>
<AF>Department of Haematology and Genetics, Prince of Wales Hospital/Sydney/Australie (1 aut., 25 aut., 26 aut., 27 aut.); Centre for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston and Harvard Medical School/Boston/Etats-Unis (2 aut.); Immunology Program, Garvan Institute of Medical Research and St Vincent's Clinical School, University of New South Wales/Sydney/Australie (3 aut., 5 aut., 6 aut., 24 aut.); Department of Human Genetics, Radboud University Nijmegen Medical Centre/Nijmegen/Pays-Bas (4 aut., 13 aut.); Division of Clinical Immunology and Allergy, Childrens Hospital Los Angeles/Etats-Unis (7 aut., 19 aut.); Department of Immunology & Infectious Diseases. Sydney Children's Hospital/Australie (8 aut., 22 aut.); Pediatric Hematology Oncology, Ospedale dei Bambini "G. Di Cristina," ARNAS Civico/Palermo/Italie (9 aut.); Institute of Human Genetics, CNRS, UPR 1142, and Université Montpellier 2/Montpellier/France (10 aut.); Department of Pediatrics, Hospital Hôtel-Dieu de France, Saint Joseph University/Beirut/Liban (11 aut.); Medical Genetics Unit, Faculty of Medicine, Saint Joseph University/Beirut/Liban (12 aut.); Faculté de Médecine René Descartes, Université Paris Descartes, Site Necker, IFR94, Paris, and Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Unité d'Immunologie et d'Hématologie Pédiatriques/Paris/France (14 aut.); Division of Immunology/Haematology/BMT and the Children's Research Centre, University Children's Hospital Zurich, and the Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich/Suisse (15 aut.); Department of Clinical Immunology, Oxford Centre for Clinical Immunology, John Radcliffe Hospital/Oxford/Royaume-Uni (16 aut.); Centre of Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg/Allemagne (17 aut.); Department of Paediatric Immunology, Newcastle General Hospital/Australie (18 aut.); Pediatric Hematology-Oncology and BMT, Hadassah University Hospital./Jerusalem/Jordanie (20 aut.); Department of Pediatrics, University of Padova/Padua/Italie (21 aut.); Department of Allergy, Immunology and Infectious Diseases, the Children's Hospital, Westmead/Sydney/Australie (23 aut.); School of Women and Children's Health, Sydney Children's Hospital and the University of New South Wales/Sydney/Australie (27 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Journal of allergy and clinical immunology; ISSN 0091-6749; Coden JACIBY; Etats-Unis; Da. 2012; Vol. 130; No. 3; Pp. 735-742; Bibl. 29 ref.</SO>
<LA>Anglais</LA>
<EA>Background: Mutations in the SP110 gene result in infantile onset of the autosomal recessive primary immunodeficiency disease veno-occlusive disease with immunodeficiency syndrome (VODI), which is characterized by hypogammaglobulinemia, T-cell dysfunction, and a high frequency of hepatic venoocclusive disease. Objectives: We sought to further characterize the clinical features, B-lineage cellular immunologic findings, and molecular pathogenesis of this disorder in 9 patients with new diagnoses, including 4 novel mutations from families of Italian, Hispanic, and Arabic ethnic origin. Methods: Methods used include clinical review; Sanger DNA sequencing of the SP110 gene; determination of transfected mutant protein function by using immunofluorescent studies in Hep-2 cells; quantitation of B-cell subsets by means of flow cytometry; assessments of B-cell function after stimulation with CD40 ligand, IL-21, or both; and differential gene expression array studies of EBV-transformed B cells. Results: We confirm the major diagnostic criteria and the clinical utility of SP110 mutation testing for the diagnosis of VODI. Analysis of 4 new alleles confirms that VODI is caused by reduced functional SP110 protein levels, Detailed B-cell immunophenotyping demonstrated that Sp110 deficiency compromises the ability of human B cells to respond to T cell- dependent stimuli and differentiate into immunoglobulin-secreting cells in vitro. Expression microarray studies have identified pathways involved in B-lymphocyte differentiation and macrophage function. Conclusion: These studies show that a range of mutations in SP110 that cause decreased SP110 protein levels and impaired late B-cell differentiation cause VODI and that the condition is not restricted to the Lebanese population.</EA>
<CC>002A06; 002B07; 002B06D01</CC>
<FD>Maladie veinoocclusive; Immunodéficit; Immunoglobulinopénie; Symptomatologie; Cellule; Homme; Association; Lymphocyte B; Multiplication cellulaire; Immunologie; Immunopathologie</FD>
<ED>Venoocclusive disease; Immune deficiency; Agammaglobulinemia; Symptomatology; Cell; Human; Association; B-Lymphocyte; Cell proliferation; Immunology; Immunopathology</ED>
<SD>Enfermedad venooclusiva; Inmunodeficiencia; Inmunoglobulinopenia; Sintomatología; Célula; Hombre; Asociación; Linfocito B; Multiplicación celular; Inmunología; Inmunopatología</SD>
<LO>INIST-2059.354000508389870230</LO>
<ID>12-0379589</ID>
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