AUTOANTIBODIES TO MALONDIALDEHYDE-MODIFIED EPITOPE IN CONNECTIVE-TISSUE DISEASES AND VASCULITIDES

Malondialdehyde (MDA), a peroxidative end-product released during poly unsaturated fatty acid degradation, reacts strongly with lysine residu es of cellular proteins. MDA-modified proteins become immunogenic and may elicit specific autoantibody formation. We hypothesized that syste mic diseases in which inflammatory events occur, could be an interesti ng model for studying oxidative stress. A few studies have suggested t hat MDA-modified proteins may exist in systemic diseases, and that aut oantibodies to MDA-modified structures might reflect this oxidative pr ocess. Autoantibodies to MDA-modified epitope(s) were therefore assaye d in sera of patients with systemic lupus erythematosus (SLE, n=29), s cleroderma (SCL, n=11), giant cell arteritis (GCA, n=11), periarteriti s nodosa (PAN, n=10), rheumatoid arthritis (RA, n=9), and healthy subj ects (HS, n=32). Significantly increased anti-MDA-modified epitope(s) autoantibodies were found in patients with SLE and also, in other syst emic diseases such as PAN and SCL. Autoantibodies to MDA-modified epit ope(s) were predominantly of IgM isotype, with low levels of IgG and n o IgA activity. In SLE, anti-MDA-modified epitope(s) autoantibody titr es correlated strongly with systemic lupus activity measure (SLAM, r=0 .702, P=0.0001), anti-nuclear antigen autoantibodies (ANA, r=0.4, P=0. 029), IgG anti-cardiolipin (r=0.558, P=0.03) and the steroid drug regi men (r=0.52, P=0.004). Autoantibodies to MDA-modified epitope(s) may r eflect oxidative modifications occurring in systemic diseases, and mig ht be useful as clinical markers of SLE activity if further investigat ed.