Design of flow cytometry panels to investigate killer immunoglobulin-like receptor expressing lymphocytes in ankylosing spondylitis
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Abstract
The major histocompatibility complex (MHC) class I molecule, Human Leukocyte Antigen B27 (HLA-B27) is a strong genetic risk factor for Ankylosing Spondylitis (AS). However, the mechanism linking HLA-B27 and the development of AS is unknown. Recent studies have shown that monoclonal antibodies targeting interleukin 17A (IL-17A) are an effective therapy for many patients with AS suggesting that IL-17A secreting lymphocytes mediate the disease. Published experimental evidence suggests further a potential role for 4 specific killer cell immunoglobulin-like receptors (KIRs) in the pathogenesis of AS, namely KIR3DL1, KIR3DL2, KIR2DL5, and KIR3DS1. KIRs are immunomodulatory receptors for MHC class I molecules that are expressed by a variety of lymphocyte subsets. We hypothesize that the expression of these AS-associated KIRs differentially modulates the expression of IL-17A in HLA-B27 positive vs. negative individuals thereby affecting susceptibility to AS. To begin to address this hypothesis, the experiments described in thesis were performed to develop a set of multi-color flow cytometry panels that permit the analysis of expression of KIR3DL1, KIR3DL2, KIR2DL5, KIR3DS1 and of IL-17A by major classical and unconventional lymphocytes subsets. These panels will be used in future studies to analyze peripheral blood samples from genotyped HLA-B27 positive and negative healthy individuals as well as from AS patients and controls.