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Blood, 1 January 2008, Vol. 111, No. 1, pp. 77-85. Prepublished online as a Blood First Edition Paper on September 26, 2007; DOI 10.1182/blood-2007-06-091744. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-06-091744v1 111/1/77    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wehr, C. Articles by Warnatz, K. Search for Related Content PubMed PubMed Citation Articles by Wehr, C. Articles by Warnatz, K. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 6, 2007 Accepted August 24, 2007 The EUROclass trial: defining subgroups in common variable immunodeficiency Claudia Wehr, Teemu Kivioja, Christian Schmitt, Berne Ferry, Torsten Witte, Efrem Eren, Marcela Vlkova, Manuel Hernandez, Drahomira Detkova, Philip R. Bos, Gonke Poerksen, Horst von Bernuth, Ulrich Baumann, Sigune Goldacker, Sylvia Gutenberger, Michael Schlesier, Florence Bergeron-van der Cruyssen, Magali Le Garff, Patrice Debre, Roland Jacobs, John Jones, Elizabeth Bateman, Jiri Litzman, P. Martin van Hagen, Alessandro Plebani, Reinhold E. Schmidt, Vojtech Thon, Isabella Quinti, Teresa Espanol, A. David Webster, Helen Chapel, Mauno Vihinen, Eric Oksenhendler, Hans Hartmut Peter, and Klaus Warnatz* Department of Rheumatology and Clinical Immunology, University Clinic Freiburg, Freiburg, Germany Institute of Medical Technology, University of Tampere, Tampere, Finland Lab.of Cellular Immunology Inserm U543, Hop. Pitie-Salpetriere and Department of Clinical Immunology, Hop. Saint-Louis, Paris, France Department of Clinical Immunology, Oxford Radcliffe Hospital Trust, Oxford, United Kingdom Department of Clinical Immunology and Rheumatology, Medical School Hanover, Hanover, Germany Department of Clinical Immunology, Royal Free Hospital, London, United Kingdom Department of Clinical Immunology and Allergology, Masaryk University, St.Anne University Hospital, Brno, Czech Republic Immunology Unit, Hospital Vall d'Hebron, Barcelona, Spain Erasmus Medical Center, Rotterdam, Netherlands Children's Hospital, Technical University Dresden, Dresden, Germany Department of Pediatric Pulmonology and Neonatology, Medical School Hanover, Hanover, Germany Department of Clinical Immunology, Oxford Radcliffe Hospital, Oxford, United Kingdom Department of Pediatrics, and the Institute for Molecular Medicine Angello Nocivelli, University of Brescia, Brescia, Italy Department of Clinical Immunology, Sapienza University, Research Unit, Rome, Italy * Corresponding author; email: klaus.warnatz{at}uniklinik-freiburg.de. The heterogeneity of common variable immunodeficiency (CVID) calls for a classification addressing pathogenic mechanisms as well as clinical relevance. This European multicenter trial was initiated to develop a consensus of two existing classification schemes based on flowcytometric B cell phenotyping and the clinical course. The clinical evaluation of 303 patients with the established diagnosis of CVID demonstrated a significant coincidence of granulomatous disease, autoimmune cytopenia and splenomegaly. Phenotyping of B cell subpopulations confirmed a severe reduction of switched memory B cells in most of the patients. This reduction was associated with a higher risk for splenomegaly and granulomatous disease. An expansion of CD21low B cells marked patients with splenomegaly. Lymphadenopathy was significantly linked with transitional B cell expansion. Based on these findings and pathogenic consideration of B cell differentiation we suggest an improved classification for CVID (EUROClass) separating patients with nearly absent B cells (<1%), severely reduced switched memory B cells (<2%) and expansion of transitional (>9%) or CD21low B cells (>10%). While the first group contains all patients with severe defects of early B cell differentiation, severely reduced switched memory B cells indicate a defective germinal center development as found in ICOS or CD40L deficiency. The underlying defects of expanded transitional or CD21low B cells remain to be elucidated. This trial is registered at http://www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html as UKF000308. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: T-cell homeostasis: the dark(ened) side of common variable immunodeficiency Antonello Giovannetti, Marina Pierdominici, and Fernando Aiuti Blood 2008 112: 446. [Full Text] [PDF] This article has been cited by other articles: C. Samarghitean, C. Ortutay, and M. Vihinen Systematic Classification of Primary Immunodeficiencies Based on Clinical, Pathological, and Laboratory Parameters J. Immunol., December 1, 2009; 183(11): 7569 - 7575. [Abstract] [Full Text] [PDF] K. Warnatz, U. Salzer, M. Rizzi, B. Fischer, S. Gutenberger, J. Bohm, A.-K. Kienzler, Q. Pan-Hammarstrom, L. Hammarstrom, M. Rakhmanov, et al. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans PNAS, August 18, 2009; 106(33): 13945 - 13950. [Abstract] [Full Text] [PDF] M. Rakhmanov, B. Keller, S. Gutenberger, C. Foerster, M. Hoenig, G. Driessen, M. van der Burg, J. J. van Dongen, E. Wiech, M. Visentini, et al. Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells PNAS, August 11, 2009; 106(32): 13451 - 13456. [Abstract] [Full Text] [PDF] A. J. Fried and F. A. Bonilla Pathogenesis, Diagnosis, and Management of Primary Antibody Deficiencies and Infections Clin. Microbiol. Rev., July 1, 2009; 22(3): 396 - 414. [Abstract] [Full Text] [PDF] U. Salzer, C. Bacchelli, S. Buckridge, Q. Pan-Hammarstrom, S. Jennings, V. Lougaris, A. Bergbreiter, T. Hagena, J. Birmelin, A. Plebani, et al. Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes Blood, February 26, 2009; 113(9): 1967 - 1976. [Abstract] [Full Text] [PDF] A. Giovannetti, M. Pierdominici, and F. Aiuti T-cell homeostasis: the dark(ened) side of common variable immunodeficiency Blood, July 15, 2008; 112(2): 446 - 446. [Full Text] [PDF] C. Wehr, H. H. Peter, and K. Warnatz Response: Improving classification in CVID Blood, July 15, 2008; 112(2): 446 - 447. [Full Text] [PDF] H. Chapel, M. Lucas, M. Lee, J. Bjorkander, D. Webster, B. Grimbacher, C. Fieschi, V. Thon, M. R. Abedi, and L. Hammarstrom Common variable immunodeficiency disorders: division into distinct clinical phenotypes Blood, July 15, 2008; 112(2): 277 - 286. [Abstract] [Full Text] [PDF] N. Rezaei, A. Aghamohammadi, S. D. Siadat, M. Moin, Z. Pourpak, M. Nejati, H. Ahmadi, S. Kamali, D. Norouzian, B. Tabaraei, et al. Serum Bactericidal Antibody Responses to Meningococcal Polysaccharide Vaccination as a Basis for Clinical Classification of Common Variable Immunodeficiency Clin. Vaccine Immunol., April 1, 2008; 15(4): 607 - 611. [Abstract] [Full Text] [PDF]

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