The EUROclass trial: defining subgroups in common variable immunodeficiency.
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.
Wehr
Claudia
C
Department of Rheumatology and Clinical Immunology, University Clinic, Freiburg, Germany.
Kivioja
Teemu
T
Schmitt
Christian
C
Ferry
Berne
B
Witte
Torsten
T
Eren
Efrem
E
Vlkova
Marcela
M
Hernandez
Manuel
M
Detkova
Drahomira
D
Bos
Philip R
PR
Poerksen
Gonke
G
von Bernuth
Horst
H
Baumann
Ulrich
U
Goldacker
Sigune
S
Gutenberger
Sylvia
S
Schlesier
Michael
M
Bergeron-van der Cruyssen
Florence
F
Le Garff
Magali
M
Debré
Patrice
P
Jacobs
Roland
R
Jones
John
J
Bateman
Elizabeth
E
Litzman
Jiri
J
van Hagen
P Martin
PM
Plebani
Alessandro
A
Schmidt
Reinhold E
RE
Thon
Vojtech
V
Quinti
Isabella
I
Espanol
Teresa
T
Webster
A David
AD
Chapel
Helen
H
Vihinen
Mauno
M
Oksenhendler
Eric
E
Peter
Hans Hartmut
HH
Warnatz
Klaus
K
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
D007136:Immunoglobulins