The EUROclass trial: defining subgroups in common variable immunodeficiency.

Research output: Contribution to journalArticle

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.

Details

Authors
  • Claudia Wehr
  • Teemu Kivioja
  • Christian Schmitt
  • Berne Ferry
  • Torsten Witte
  • Efrem Eren
  • Marcela Vlkova
  • Manuel Hernandez
  • Drahomira Detkova
  • Philip R Bos
  • Gonke Poerksen
  • Horst von Bernuth
  • Ulrich Baumann
  • Sigune Goldacker
  • Sylvia Gutenberger
  • Michael Schlesier
  • Florence Bergeron-van der Cruyssen
  • Magali Le Garff
  • Patrice Debré
  • Roland Jacobs
  • John Jones
  • Elizabeth Bateman
  • Jiri Litzman
  • P Martin van Hagen
  • Alessandro Plebani
  • Reinhold E Schmidt
  • Vojtech Thon
  • Isabella Quinti
  • Teresa Espanol
  • A David Webster
  • Helen Chapel
  • Eric Oksenhendler
  • Hans Hartmut Peter
  • Klaus Warnatz
External organisations
  • Tampere University Hospital
  • University of Tampere
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology

Keywords

  • B-Lymphocytes: immunology, B-Lymphocytes: pathology, Common Variable Immunodeficiency: classification, Common Variable Immunodeficiency: epidemiology, Common Variable Immunodeficiency: immunology, Common Variable Immunodeficiency: pathology, Europe: epidemiology, Homeostasis: immunology, Immunoglobulins: blood
Original languageEnglish
Pages (from-to)77-85
JournalBlood
Volume111
Issue number1
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes