The EUROclass trial: defining subgroups in common variable immunodeficiency

C Wehr, T Kivioja, C Schmitt, B Ferry, T de Witte, E Eren, M Vlkova, M Hernandez, D Detkova, PR (Philip) Bos, G Poerksen, H von Bemuth, U Baumann, S Goldacker, S Gutenberger, M Schlesier, BVDC Florence, M Le Garff, P Debre, R JacobsJ Jones, E Bateman, J Litzman, P.M. van Hagen, A Plebani, RE Schmidt, V Thon, I Quinti, T Espanol, AD Webster, H Chapel, M Vihinen, E Oksenhendler, HH Peter, K Warnatz

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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 as UKF000308.
Original languageUndefined/Unknown
Pages (from-to)77-85
Number of pages9
Issue number1
Publication statusPublished - 2008

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