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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3045-3052. Prepublished online as a Blood First Edition Paper on December 29, 2005; DOI 10.1182/blood-2005-07-2955. This Article Full Text (PDF) Supplemental Table All Versions of this Article: 2005-07-2955v1 107/8/3045    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Warnatz, K. Articles by Grimbacher, B. Search for Related Content PubMed PubMed Citation Articles by Warnatz, K. Articles by Grimbacher, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 22, 2005 Accepted October 7, 2005 Human ICOS-deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency Klaus Warnatz, Lukas Bossaller, Ulrich Salzer, Andrea Skrabl-Baumgartner, Wolfgang Schwinger, Mirjam van der Burg, Jaques J van Dongen, Marzenna Orlowska-Volk, Rolf Knoth, Anne Durandy, Ruth Draeger, Michael Schlesier, Hans-Hartmut Peter, and Bodo Grimbacher* Division of Rheumatology and Clinical Immunology, Dept. of Medicine, University Hospital, Freiburg, Germany Dept. of Pediatrics Division of Hematology/Oncology, University Hospital Graz, Graz, Austria Dept. of Immunology, Unit Molecular Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands Dept. of Pathology, University Hospital, Freiburg, Germany Dept. of Neuropathology, University Hospital, Freiburg, Germany INSERM U 429, Hopital Necker, Paris, France * Corresponding author; email: grimbacher{at}medizin.ukl.uni-freiburg.de. The homozygous deletion of the "Inducible Co-Stimulator" (ICOS), an activation-induced member of the CD28 family on T cells, causes an antibody deficiency syndrome in affected humans. The identification of a total of nine ICOS-deficient patients revealed that this monogenic disease comprises the full clinical phenotype described for common variable immunodeficiency (CVID), including recurrent bacterial infections, adult as well as childhood onset, splenomegaly, autoimmune phenomena (autoimmune neutropenia), intestinal lymphoid hyperplasia and malignancy (carcinoma of the vulva). All patients exhibited a profound hypogammaglobulinemia and a disturbed B cell homeostasis. The severe reduction of class-switched memory B cells resulted from poor germinal center formation in the absence of ICOS. The additional decrease of naive B cells was associated with a partial inhibition of the early B cell development at the pre B-I stage. T cell homeostasis seemed to be not affected, but low IL-10 production by ICOS-deficient T cells may contribute to the disturbed germinal center reaction. Human ICOS-deficiency is indistinguishable from CVID and thus serves as a monogenic model for this complex syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. C. Cook and S. G. Tangye Primary immune deficiencies affecting lymphocyte differentiation: lessons from the spectrum of resulting infections Int. Immunol., September 1, 2009; 21(9): 1003 - 1011. [Abstract] [Full Text] [PDF] M Her, D Kim, M Oh, H Jeong, and I Choi Increased expression of soluble inducible costimulator ligand (ICOSL) in patients with systemic lupus erythematosus Lupus, May 1, 2009; 18(6): 501 - 507. [Abstract] [PDF] N. Takahashi, K. Matsumoto, H. Saito, T. Nanki, N. Miyasaka, T. Kobata, M. Azuma, S.-K. Lee, S. Mizutani, and T. 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