The EUROclass trial: defining subgroups in common variable immunodeficiency.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3635223
- author
- publishing date
- 2008
- 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}}, }