Many autoimmune conditions are believed to result from chronic inflammation as a consequence of the interaction of genetic and environmental factors in susceptible individuals. One common feature in some autoimmune diseases is the decrease in terminal galactosylation of the constant region N-glycan of the total plasma immunoglobulin. The glycosylation pattern of the antibodies isolated from patients with ANCA-MPO (a kidney autoimmune disease) is being investigated to determine whether a similar trend is observed in individuals with other autoimmune disorders as we have seen before. A protocol for isolation of the antibody followed by SDS-PAGE, digestion, and LC/MS analyses is being developed. Structural and functional studies of the autoantigens are necessary to increase our understanding of the pathogenesis of Sjogrens syndrome. The function(s) of the primary autoantigen, LaSSB, associated with Sjogrens syndrome, a chronic rheumatic autoimmune disease that primarily targets the salivary and lacrimal glands, is unknown at this time, but the role of the LaSSB antigen is thought to be critical for understanding the mechanism of the development of autoimmunity. Structural and functional studies of this antigen are necessary to increase our understanding of the pathogenesis of Sjogrens syndrome. Structural studies involving chemical modification, oxidative footprinting, and H/D exchange in combination with mass spectrometric analyses have been used to gain information regarding the surface accessibility of amino acids in LaSSB. Collectively, these data provide useful information regarding the tertiary structures of LaSSB and has been used to help generate a structural model of the full-length LaSSB. The glycosylation pattern of antibodies and antigens isolated from patients with ANCA-MPO and ANCA-PR3 (kidney autoimmune diseases) are being investigated. In PR3-ANCA disease, N-linked oligosaccharides deficient in terminal sialic acid and galactose (IgG-G0 glycan form) is significantly increased and the high incidence of IgG-G0 in serum correlates with disease activity. ANCA-MPO sera is investigated to determine whether there is a similar pattern of abnormal IgG glycosylation observed and whether that correlates with disease activity.
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