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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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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
ISSN
1528-0020
DOI
10.1182/blood-2007-06-091744
language
English
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no
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9144ef58-5d20-4a16-ba5c-09722a53176f (old id 3635223)
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http://www.ncbi.nlm.nih.gov/pubmed/17898316?dopt=Abstract
date added to LUP
2013-06-12 16:27:32
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2017-11-19 04:17:21
@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},
  keyword      = {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},
  volume       = {111},
  year         = {2008},
}