alexa Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency.
Immunology

Immunology

Journal of Clinical & Cellular Immunology

Author(s): Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K,

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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. This article was published in Nat Immunol and referenced in Journal of Clinical & Cellular Immunology

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