The EUROclass trial: defining subgroups in common variable immunodeficiency.

• Authors: WEHR Claudia; KIVIOJA Teemu; SCHMITT Christian; FERRY Berne; WITTE Torsten; EREN Efrem; VLKOVA Marcela; HERNANDEZ Manuel; DEDKOVA Drahomíra; BOS Philip R.; POERKSEN Gonke; VON BEMUTH Horst; BAUMANN Ulrich; GOLDACKER Sigune; GUTENBERGER Sylvia; SCHLESIER Michael; BERGERON-VAN DER CRUYSSEN Florence; LE GARFF Magali; DEBRÉ Patrice; JACOBS Roland; JONES John; BATERMAN Elizabeth; LITZMAN Jiří; VAN HAGEN P. Martin; PLEBANI Alessandro; SCHMIDT Reinhold E.; THON Vojtěch; QUINTI Isabella; ESPANOL Teresa; WEBSTER A. David; CHAPEL Helen; VIHINEN Mauno; OKSENHENDLER Eric; PETER Hans Hartmut; WARNATZ Klaus
• Year of publication: 2008
• Type: Article in Periodical
• Magazine / Source: Blood
• MU Faculty or unit: Faculty of Medicine
• Field: Immunology
• Keywords: common variable immunodefciency; B-lymphocytes; classification
• Description: 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.