Investigate Pathogenic Role of Rheumatoid Arthritis, Sjogren$S Syndrome, Systemic Lupus Erythematosus and Its Combined Syndromes from Post-Translational Modification of Serum Proteins: Study of Malondialdehyde Modification

Primary Sjogren's syndrome (pSS), systemic lupus erythematosus (SLE) and its combined syndromes are autoimmune diseases. Primary Sjogren's syndrome occurs by itself, and secondary Sjogren's syndrome (sSS) occurs with Rheumatoid arthritis (RA-sSS) and SLE (SLE-sSS). In chronic inflammation, oxidative stress generated ROS (reactive oxygen species) to cause lipid peroxidation by the depletion of unsaturated fatty acids of the cell membrane to produce malondialdehyde (MDA), that is end-product of peroxidized ω-6 polyunsaturated fatty acids. MDA can attack protein formed covalently-bonded adducts by reacting with lysine, histidine, glutamine, asparagine and arginine residues. Autoantibody isotypes against MDA-protein adducts show high immunogenicity in diseases including RA, SLE, atherosclerosis、peripheral artery disease, myocardial infarction, coronary artery disease, systemic vasculitis and diabetes. In preliminary research, we found novel differentially expressed Con A-bound serum proteins and MDA-ptpide adducts in patients with pSS and autoantibody istypes against MDA-peptide adducts in patients with pSS and SLE. In this study, we will investigate novel MDA-protein adducts and it's role in the pathogenesis of the pSS, SLE and its combined syndromes. The study goals of year 1 are identification and validation of novel MDA-modified differentially expressed Con A-bound proteins, preparation and validation of MDA-modified peptide, quantitative analysis of MDA-protein adducts and autoantibody isotypes examination against MDA-modified peptides in serum from healthy control, pSS, RA-sSS and RA. The study goals of year 2 are identification and validation of novel MDA-protein adducts and MDA-modified differentially expressed Con A-bound proteins, preparation and validation of MDA-modified peptide, quantitative analysis of MDA-protein adducts and autoantibody isotypes examination against MDA-modified peptides in serum from healthy control, SLE, SLE-sSS and pSS.