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  • Title: Polymorphisms in the 2q33 and 3q21 chromosome regions including T-cell coreceptor and ligand genes may influence susceptibility to pemphigus foliaceus.
    Author: Dalla-Costa R, Pincerati MR, Beltrame MH, Malheiros D, Petzl-Erler ML.
    Journal: Hum Immunol; 2010 Aug; 71(8):809-17. PubMed ID: 20433886.
    Abstract:
    Signaling through antigen presenting cells is required to activate T lymphocytes. The antigen-specific signal is given by interaction of the T-cell receptor (TCR) with the major histocompatibility complex (MHC)/peptide complex. Also essential for activation is the interaction of the coreceptor CD28 with ligands of the B7 family (CD80 and CD86) on antigen presenting cells. Coreceptor CTLA-4 is a negative regulator and binds the same B7 isoforms, contributing to immunologic homeostasis and peripheral tolerance. CD28 and CTLA4 are homologous and closely linked genes in 2q33, as are CD80 and CD86 in the 3q21 chromosomal region. Pemphigus foliaceus (PF) is a multifactorial autoimmune blistering disease characterized by keratinocyte detachment and by autoantibodies against desmoglein 1, a desmosomal protein. To investigate the involvement of CD28, CTLA4, CD80, and CD86 genes in PF pathogenesis, 18 polymorphisms in 2q33 and 3q21 chromosomal regions were analyzed in 269 patients and 395 controls subdivided according to predominant ancestry in Euro-Brazilian and Afro-Brazilian individuals. Associations were found with CD86 1057G>A, CTLA4-1722T>C, CTLA4-318C>T, CTLA4(AT)n, CD28(CAA)n, and D2S72(CA)n. There is no evidence of gene-gene interactions. We conclude that polymorphisms in the 2q33 and 3q21 chromosomal regions may influence PF disease susceptibility, most likely affecting CTLA4 and possibly inducible T-cell costimulator, (ICOS) expression, and also CD86 function.
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