Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/31325 http://dx.doi.org/10.1182/blood-2008-02-141937 |
Resumo: | TNFRSF13B encodes transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a B cell specific tumor necrosis factor (TNF) receptor superfamily member. Both biallelic and monoallelic TNFRSF13B mutations were identified in patients with common variable immunodeficiency disorders. the genetic complexity and variable clinical presentation of TACI deficiency prompted us to evaluate the genetic, immunologic, and clinical condition in 50 individuals with TNFRSF13B alterations, following screening of 564 unrelated patients with hypogammaglobulinemia. We identified 13 new sequence variants. the most frequent TNFRSF13B variants (C104R and A181E; n = 39; 6.9%) were also present in a heterozygous state in 2% of 675 controls. All patients with biallelic mutations had hypogammaglobulinemia and nearly all showed impaired binding to a proliferation-inducing ligand (APRIL). However, the majority (n = 41; 82%) of the patients carried monoallelic changes in TNFRSF13B. Presence of a heterozygous mutation was associated with antibody deficiency (P < .001, relative risk 3.6). Heterozygosity for the most common mutation, C104R, was associated with disease (P < .001, relative risk 4.2). Furthermore, heterozygosity for C104R was associated with low numbers of IgD(-)CD27(+) B cells (P = .019), benign lymphoproliferation (P < .001), and autoimmune complications (P = .001). These associations indicate that C104R heterozygosity increases the risk for common variable immunodeficiency disorders and influences clinical presentation. (Blood. 2009; 113: 1967-1976) |
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Salzer, UlrichBacchelli, ChiaraBuckridge, SylviePan-Hammarstrom, QiangJennings, StephanieLougaris, VassilisBergbreiter, AstridHagena, TinaBirmelin, JenniferPlebani, AlessandroWebster, A. David B.Peter, Hans-HartmutSuez, DanielChapel, HelenMcLean-Tooke, AndrewSpickett, Gavin P.Anover-Sombke, StephanieOchs, Hans D.Urschel, SimonBelohradsky, Bernd H.Ugrinovic, SanjaKumararatne, Dinakantha S.Lawrence, Tatiana C. [UNIFESP]Holm, Are M.Franco, Jose L.Schulze, IlkaSchneider, PascalGertz, E. MichaelSchaffer, Alejandro A.Hammarstrom, LennartThrasher, Adrian J.Gaspar, H. BobbyGrimbacher, BodoUniv Hosp FreiburgInst Child HlthKarolinska Univ Hosp HuddingeUniv BresciaSpedali Civil BresciaRoyal Free HospUCLAllergy Asthma & Immunol ClinOxford Radcliffe HospRoyal Victoria InfirmUniv WashingtonChildrens HospUniv MunichAddenbrookes HospUniversidade Federal de São Paulo (UNIFESP)Univ OsloUniv AntioquiaCharite Humboldt UnivUniv LausanneNatl Lib Med2016-01-24T13:52:17Z2016-01-24T13:52:17Z2009-02-26Blood. Washington: Amer Soc Hematology, v. 113, n. 9, p. 1967-1976, 2009.0006-4971http://repositorio.unifesp.br/handle/11600/31325http://dx.doi.org/10.1182/blood-2008-02-14193710.1182/blood-2008-02-141937WOS:000263723700014TNFRSF13B encodes transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a B cell specific tumor necrosis factor (TNF) receptor superfamily member. Both biallelic and monoallelic TNFRSF13B mutations were identified in patients with common variable immunodeficiency disorders. the genetic complexity and variable clinical presentation of TACI deficiency prompted us to evaluate the genetic, immunologic, and clinical condition in 50 individuals with TNFRSF13B alterations, following screening of 564 unrelated patients with hypogammaglobulinemia. We identified 13 new sequence variants. the most frequent TNFRSF13B variants (C104R and A181E; n = 39; 6.9%) were also present in a heterozygous state in 2% of 675 controls. All patients with biallelic mutations had hypogammaglobulinemia and nearly all showed impaired binding to a proliferation-inducing ligand (APRIL). However, the majority (n = 41; 82%) of the patients carried monoallelic changes in TNFRSF13B. Presence of a heterozygous mutation was associated with antibody deficiency (P < .001, relative risk 3.6). Heterozygosity for the most common mutation, C104R, was associated with disease (P < .001, relative risk 4.2). Furthermore, heterozygosity for C104R was associated with low numbers of IgD(-)CD27(+) B cells (P = .019), benign lymphoproliferation (P < .001), and autoimmune complications (P = .001). These associations indicate that C104R heterozygosity increases the risk for common variable immunodeficiency disorders and influences clinical presentation. (Blood. 2009; 113: 1967-1976)Deutsche Forschungsgemeinschaft (Bonn, Germany)European Commission (Brussels, Belgium)National Institutes of Health/National Institute of Allergy and Infectious DiseasesPrimary Immunodeficiency Association (PIA; London, United Kingdom)Medical Research Council (MRC; London, United Kingdom)The Wellcome Trust (London, United Kingdom)Swedish Research Council (Stockholm, Sweden)Fondazione C. Golgi (Brescia, Italy)Swiss National Science Foundation (Bern, Switzerland)Grant Colciencias (Bogota, Colombia)NIHJeffrey Modell Foundation (New York, NY)Intramural Research Program of the National Institutes of Health, National Library of MedicineUniv Hosp Freiburg, Dept Rheumatol & Clin Immunol, Freiburg, GermanyInst Child Hlth, Mol Immunol Unit, London, EnglandKarolinska Univ Hosp Huddinge, Karolinska Inst, Div Clin Immunol, Stockholm, SwedenUniv Brescia, Pediat Clin, Brescia, ItalySpedali Civil Brescia, Ist Med Mol Angelo Nocivelli, I-25125 Brescia, ItalyRoyal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, EnglandUCL, London, EnglandAllergy Asthma & Immunol Clin, Irving, TX USAOxford Radcliffe Hosp, Nuffield Dept Med, Oxford, EnglandRoyal Victoria Infirm, Dept Immunol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, EnglandUniv Washington, Reg Med Ctr, Seattle, WA 98195 USAChildrens Hosp, Seattle, WA USAUniv Munich, Div Infect Dis & Immunol, Univ Childrens Hosp, Munich, GermanyAddenbrookes Hosp, Dept Clin Immunol, Cambridge, EnglandUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilUniv Oslo, Natl Hosp, Internal Med Res Inst, Oslo, NorwayUniv Antioquia, Grp Immunodeficiencias Primarias, Medellin, ColombiaCharite Humboldt Univ, Dept Paediat Pneumol & Immunol, Berlin, GermanyUniv Lausanne, Dept Biochem, Lausanne, SwitzerlandNatl Lib Med, Natl Ctr Biotechnol Informat, NIH, US Dept HHS, Bethesda, MD 20894 USAUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilDeutsche Forschungsgemeinschaft (Bonn, Germany): GR1617/3Deutsche Forschungsgemeinschaft (Bonn, Germany): SFB620/C2Deutsche Forschungsgemeinschaft (Bonn, Germany): SFB620/Z1Deutsche Forschungsgemeinschaft (Bonn, Germany): SFB620/C1European Commission (Brussels, Belgium): SP23-CT-2005-006411European Commission (Brussels, Belgium): MEXT-CT-2006-042316European Commission (Brussels, Belgium): HEALTH-F2-2008-201549National Institutes of Health/National Institute of Allergy and Infectious Diseases: NO1-A130070Fondazione C. Golgi (Brescia, Italy): PRIN2006Grant Colciencias (Bogota, Colombia): 1115-05-16784NIH: HD 37091Web of Science1967-1976engAmer Soc HematologyBloodRelevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/313252022-09-27 10:14:37.855metadata only accessoai:repositorio.unifesp.br:11600/31325Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T13:14:37Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes |
title |
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes |
spellingShingle |
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes Salzer, Ulrich |
title_short |
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes |
title_full |
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes |
title_fullStr |
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes |
title_full_unstemmed |
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes |
title_sort |
Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes |
author |
Salzer, Ulrich |
author_facet |
Salzer, Ulrich Bacchelli, Chiara Buckridge, Sylvie Pan-Hammarstrom, Qiang Jennings, Stephanie Lougaris, Vassilis Bergbreiter, Astrid Hagena, Tina Birmelin, Jennifer Plebani, Alessandro Webster, A. David B. Peter, Hans-Hartmut Suez, Daniel Chapel, Helen McLean-Tooke, Andrew Spickett, Gavin P. Anover-Sombke, Stephanie Ochs, Hans D. Urschel, Simon Belohradsky, Bernd H. Ugrinovic, Sanja Kumararatne, Dinakantha S. Lawrence, Tatiana C. [UNIFESP] Holm, Are M. Franco, Jose L. Schulze, Ilka Schneider, Pascal Gertz, E. Michael Schaffer, Alejandro A. Hammarstrom, Lennart Thrasher, Adrian J. Gaspar, H. Bobby Grimbacher, Bodo |
author_role |
author |
author2 |
Bacchelli, Chiara Buckridge, Sylvie Pan-Hammarstrom, Qiang Jennings, Stephanie Lougaris, Vassilis Bergbreiter, Astrid Hagena, Tina Birmelin, Jennifer Plebani, Alessandro Webster, A. David B. Peter, Hans-Hartmut Suez, Daniel Chapel, Helen McLean-Tooke, Andrew Spickett, Gavin P. Anover-Sombke, Stephanie Ochs, Hans D. Urschel, Simon Belohradsky, Bernd H. Ugrinovic, Sanja Kumararatne, Dinakantha S. Lawrence, Tatiana C. [UNIFESP] Holm, Are M. Franco, Jose L. Schulze, Ilka Schneider, Pascal Gertz, E. Michael Schaffer, Alejandro A. Hammarstrom, Lennart Thrasher, Adrian J. Gaspar, H. Bobby Grimbacher, Bodo |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Univ Hosp Freiburg Inst Child Hlth Karolinska Univ Hosp Huddinge Univ Brescia Spedali Civil Brescia Royal Free Hosp UCL Allergy Asthma & Immunol Clin Oxford Radcliffe Hosp Royal Victoria Infirm Univ Washington Childrens Hosp Univ Munich Addenbrookes Hosp Universidade Federal de São Paulo (UNIFESP) Univ Oslo Univ Antioquia Charite Humboldt Univ Univ Lausanne Natl Lib Med |
dc.contributor.author.fl_str_mv |
Salzer, Ulrich Bacchelli, Chiara Buckridge, Sylvie Pan-Hammarstrom, Qiang Jennings, Stephanie Lougaris, Vassilis Bergbreiter, Astrid Hagena, Tina Birmelin, Jennifer Plebani, Alessandro Webster, A. David B. Peter, Hans-Hartmut Suez, Daniel Chapel, Helen McLean-Tooke, Andrew Spickett, Gavin P. Anover-Sombke, Stephanie Ochs, Hans D. Urschel, Simon Belohradsky, Bernd H. Ugrinovic, Sanja Kumararatne, Dinakantha S. Lawrence, Tatiana C. [UNIFESP] Holm, Are M. Franco, Jose L. Schulze, Ilka Schneider, Pascal Gertz, E. Michael Schaffer, Alejandro A. Hammarstrom, Lennart Thrasher, Adrian J. Gaspar, H. Bobby Grimbacher, Bodo |
description |
TNFRSF13B encodes transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a B cell specific tumor necrosis factor (TNF) receptor superfamily member. Both biallelic and monoallelic TNFRSF13B mutations were identified in patients with common variable immunodeficiency disorders. the genetic complexity and variable clinical presentation of TACI deficiency prompted us to evaluate the genetic, immunologic, and clinical condition in 50 individuals with TNFRSF13B alterations, following screening of 564 unrelated patients with hypogammaglobulinemia. We identified 13 new sequence variants. the most frequent TNFRSF13B variants (C104R and A181E; n = 39; 6.9%) were also present in a heterozygous state in 2% of 675 controls. All patients with biallelic mutations had hypogammaglobulinemia and nearly all showed impaired binding to a proliferation-inducing ligand (APRIL). However, the majority (n = 41; 82%) of the patients carried monoallelic changes in TNFRSF13B. Presence of a heterozygous mutation was associated with antibody deficiency (P < .001, relative risk 3.6). Heterozygosity for the most common mutation, C104R, was associated with disease (P < .001, relative risk 4.2). Furthermore, heterozygosity for C104R was associated with low numbers of IgD(-)CD27(+) B cells (P = .019), benign lymphoproliferation (P < .001), and autoimmune complications (P = .001). These associations indicate that C104R heterozygosity increases the risk for common variable immunodeficiency disorders and influences clinical presentation. (Blood. 2009; 113: 1967-1976) |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-02-26 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:52:17Z |
dc.date.available.fl_str_mv |
2016-01-24T13:52:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Blood. Washington: Amer Soc Hematology, v. 113, n. 9, p. 1967-1976, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/31325 http://dx.doi.org/10.1182/blood-2008-02-141937 |
dc.identifier.issn.none.fl_str_mv |
0006-4971 |
dc.identifier.doi.none.fl_str_mv |
10.1182/blood-2008-02-141937 |
dc.identifier.wos.none.fl_str_mv |
WOS:000263723700014 |
identifier_str_mv |
Blood. Washington: Amer Soc Hematology, v. 113, n. 9, p. 1967-1976, 2009. 0006-4971 10.1182/blood-2008-02-141937 WOS:000263723700014 |
url |
http://repositorio.unifesp.br/handle/11600/31325 http://dx.doi.org/10.1182/blood-2008-02-141937 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Blood |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1967-1976 |
dc.publisher.none.fl_str_mv |
Amer Soc Hematology |
publisher.none.fl_str_mv |
Amer Soc Hematology |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764167273250816 |