| |
|
|
|
|
|
|
|||
|
Blood, 1 January 2008, Vol. 111, No. 1, pp. 77-85. Prepublished online as a Blood First Edition Paper on September 26, 2007; DOI 10.1182/blood-2007-06-091744.
CLINICAL TRIALS AND OBSERVATIONS The EUROclass trial: defining subgroups in common variable immunodeficiency1 Department of Rheumatology and Clinical Immunology, University Clinic, Freiburg, Germany; 2 Institute of Medical Technology, University of Tampere, Tampere, Finland; 3 Laboratory of Cellular Immunology, Inserm U543, Hôpital Pitié-Salpétrière and Department of Clinical Immunology, Hôpital St Louis, Paris, France; 4 Department of Clinical Immunology, Oxford Radcliffe Hospital Trust, Oxford, United Kingdom; 5 Department of Clinical Immunology and Rheumatology, Medical School Hannover, Hannover, Germany; 6 Department of Clinical Immunology, Royal Free Hospital, London, United Kingdom; 7 Department of Clinical Immunology and Allergology, Masaryk University, St Anne University Hospital, Brno, Czech Republic; 8 Immunology Unit, Hospital Vall d'Hebron, Barcelona, Spain; 9 Erasmus Medical Center, Rotterdam, the Netherlands; 10 Children's Hospital, Technical University Dresden, Dresden, Germany; 11 Department of Pediatric Pulmonology and Neonatology, Medical School Hannover, Hannover, Germany; 12 Department of Pediatrics and Institute for Molecular Medicine Angello Nocivelli, University of Brescia, Brescia, Italy; 13 Department of Clinical Immunology, Sapienza University, Research Unit, Rome, Italy; and 14 Tampere University Hospital, Tampere, Finland 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 CD21low 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 CD21low 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 CD21low B cells remain to be elucidated. This trial is re-gistered at http://www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html as UKF000308.
Related Article in Blood Online:
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Copyright © 2008 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||