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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 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 Citation Map 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 Immunobiology Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS The EUROclass trial: defining subgroups in common variable immunodeficiency Claudia Wehr1, Teemu Kivioja2, Christian Schmitt3, Berne Ferry4, Torsten Witte5, Efrem Eren6, Marcela Vlkova7, Manuel Hernandez8, Drahomira Detkova8, Philip R. Bos9, Gonke Poerksen10, Horst von Bernuth10, Ulrich Baumann11, Sigune Goldacker1, Sylvia Gutenberger1, Michael Schlesier1, Florence Bergeron-van der Cruyssen3, Magali Le Garff3, Patrice Debré3, Roland Jacobs5, John Jones4, Elizabeth Bateman4, Jiri Litzman7, P. Martin van Hagen9, Alessandro Plebani12, Reinhold E. Schmidt5, Vojtech Thon7, Isabella Quinti13, Teresa Espanol8, A. David Webster6, Helen Chapel4, Mauno Vihinen2,14, Eric Oksenhendler3, Hans Hartmut Peter1, and Klaus Warnatz1 1 Department of Rheumatology and Clinical Immunology, University Clinic, Freiburg, Germany; 2 Institute of Medical Technology, University of Tampere, Tampere, Finland; 3 Laboratory of Cellular Immunology, Inserm U543, Hôpital Pitié-Salpétrière and Department of Clinical Immunology, Hôpital St Louis, Paris, France; 4 Department of Clinical Immunology, Oxford Radcliffe Hospital Trust, Oxford, United Kingdom; 5 Department of Clinical Immunology and Rheumatology, Medical School Hannover, Hannover, Germany; 6 Department of Clinical Immunology, Royal Free Hospital, London, United Kingdom; 7 Department of Clinical Immunology and Allergology, Masaryk University, St Anne University Hospital, Brno, Czech Republic; 8 Immunology Unit, Hospital Vall d'Hebron, Barcelona, Spain; 9 Erasmus Medical Center, Rotterdam, the Netherlands; 10 Children's Hospital, Technical University Dresden, Dresden, Germany; 11 Department of Pediatric Pulmonology and Neonatology, Medical School Hannover, Hannover, Germany; 12 Department of Pediatrics and Institute for Molecular Medicine Angello Nocivelli, University of Brescia, Brescia, Italy; 13 Department of Clinical Immunology, Sapienza University, Research Unit, Rome, Italy; and 14 Tampere University Hospital, Tampere, Finland 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 2 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 that 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 (less than 1%), severely reduced switched memory B cells (less than 2%), and expansion of transitional (more than 9%) or CD21low B cells (more than 10%). Whereas 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 inducible constimulator (ICOS) or CD40L deficiency. The underlying defects of expanded transitional or CD21low B cells remain to be elucidated. This trial is re-gistered 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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