title: Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency.
abstract: No genetic defect is known to cause common variable immunodeficiency (CVID), a heterogeneous human disorder leading to adult-onset panhypogammaglobulinemia. In a search for CVID candidate proteins, we found four of 32 patients to lack ICOS, the "inducible costimulator" on activated T cells, due to an inherited homozygous deletion in the ICOS gene. T cells from these individuals were normal with regard to subset distribution, activation, cytokine production and proliferation. In contrast, naive, switched and memory B cells were reduced. The phenotype of human ICOS deficiency, which differs in key aspects from that of the ICOS-/- mouse, suggests a critical involvement of ICOS in T cell help for late B cell differentiation, class-switching and memory B cell generation.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Medical School, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
authors.forename: Michael
authors.initials: M
authors.lastname: Schlesier
authors.forename: Erik
authors.initials: E
authors.lastname: Glocker
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.forename: Ruth
authors.initials: R
authors.lastname: Dräger
authors.forename: Hermann
authors.initials: H
authors.lastname: Eibel
authors.forename: Beate
authors.initials: B
authors.lastname: Fischer
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Hans W
authors.initials: HW
authors.lastname: Mages
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kroczek
authors.forename: Hans H
authors.initials: HH
authors.lastname: Peter
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001402:B-Lymphocytes / Q000502:physiology; D018106:CD28 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007156:Immunologic Memory / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; C556692:ICOS protein, human; C556694:Icos protein, mouse; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D060889:Inducible T-Cell Co-Stimulator Protein; D011948:Receptors, Antigen, T-Cell