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The EUROclass trial: defining subgroups in common variable immunodeficiency.

Wehr, Claudia ; Kivioja, Teemu ; Schmitt, Christian ; Ferry, Berne ; Witte, Torsten ; Eren, Efrem ; Vlkova, Marcela ; Hernandez, Manuel ; Detkova, Drahomira and Bos, Philip R , et al. (2008) In Blood 111(1). p.77-85
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
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
in
Blood
volume
111
issue
1
pages
77 - 85
publisher
American Society of Hematology
external identifiers
  • pmid:17898316
  • scopus:38049105639
  • pmid:17898316
ISSN
1528-0020
DOI
10.1182/blood-2007-06-091744
language
English
LU publication?
no
id
9144ef58-5d20-4a16-ba5c-09722a53176f (old id 3635223)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/17898316?dopt=Abstract
date added to LUP
2016-04-04 07:52:44
date last changed
2022-04-23 08:39:56
@article{9144ef58-5d20-4a16-ba5c-09722a53176f,
  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.}},
  author       = {{Wehr, Claudia and Kivioja, Teemu and Schmitt, Christian and Ferry, Berne and Witte, Torsten and Eren, Efrem and Vlkova, Marcela and Hernandez, Manuel and Detkova, Drahomira and Bos, Philip R and Poerksen, Gonke and von Bernuth, Horst and Baumann, Ulrich and Goldacker, Sigune and Gutenberger, Sylvia and Schlesier, Michael and Bergeron-van der Cruyssen, Florence and Le Garff, Magali and Debré, Patrice and Jacobs, Roland and Jones, John and Bateman, Elizabeth and Litzman, Jiri and van Hagen, P Martin and Plebani, Alessandro and Schmidt, Reinhold E and Thon, Vojtech and Quinti, Isabella and Espanol, Teresa and Webster, A David and Chapel, Helen and Vihinen, Mauno and Oksenhendler, Eric and Peter, Hans Hartmut and Warnatz, Klaus}},
  issn         = {{1528-0020}},
  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}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{77--85}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{The EUROclass trial: defining subgroups in common variable immunodeficiency.}},
  url          = {{http://dx.doi.org/10.1182/blood-2007-06-091744}},
  doi          = {{10.1182/blood-2007-06-091744}},
  volume       = {{111}},
  year         = {{2008}},
}