title: The EUROclass trial: defining subgroups in common variable immunodeficiency.
abstract: 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 CD21(low) 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 CD21(low) 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 CD21(low) B cells remain to be elucidated. This trial is re-gistered at http://www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html as UKF000308.
authors: Department of Rheumatology and Clinical Immunology, University Clinic, Freiburg, Germany.
authors: Claudia
authors: C
authors: Wehr
authors: Teemu
authors: T
authors: Kivioja
authors: Christian
authors: C
authors: Schmitt
authors: Berne
authors: B
authors: Ferry
authors: Torsten
authors: T
authors: Witte
authors: Efrem
authors: E
authors: Eren
authors: Marcela
authors: M
authors: Vlkova
authors: Manuel
authors: M
authors: Hernandez
authors: Drahomira
authors: D
authors: Detkova
authors: Philip R
authors: PR
authors: Bos
authors: Gonke
authors: G
authors: Poerksen
authors: Horst
authors: H
authors: von Bernuth
authors: Ulrich
authors: U
authors: Baumann
authors: Sigune
authors: S
authors: Goldacker
authors: Sylvia
authors: S
authors: Gutenberger
authors: Michael
authors: M
authors: Schlesier
authors: Florence
authors: F
authors: Bergeron-van der Cruyssen
authors: Magali
authors: M
authors: Le Garff
authors: Patrice
authors: P
authors: Debré
authors: Roland
authors: R
authors: Jacobs
authors: John
authors: J
authors: Jones
authors: Elizabeth
authors: E
authors: Bateman
authors: Jiri
authors: J
authors: Litzman
authors: P Martin
authors: PM
authors: van Hagen
authors: Alessandro
authors: A
authors: Plebani
authors: Reinhold E
authors: RE
authors: Schmidt
authors: Vojtech
authors: V
authors: Thon
authors: Isabella
authors: I
authors: Quinti
authors: Teresa
authors: T
authors: Espanol
authors: A David
authors: AD
authors: Webster
authors: Helen
authors: H
authors: Chapel
authors: Mauno
authors: M
authors: Vihinen
authors: Eric
authors: E
authors: Oksenhendler
authors: Hans Hartmut
authors: HH
authors: Peter
authors: Klaus
authors: K
authors: Warnatz
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015331:Cohort Studies; D017074:Common Variable Immunodeficiency / Q000145:classification* / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D032921:Consensus; D005060:Europe / Q000453:epidemiology; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged
chemical_list: D007136:Immunoglobulins