Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides.
Malondialdehyde (MDA), a peroxidative end-product released during polyunsaturated fatty acid degradation, reacts strongly with lysine residues of cellular proteins. MDA-modified proteins become immunogenic and may elicit specific autoantibody formation. We hypothesized that systemic diseases in which inflammatory events occur, could be an interesting model for studying oxidative stress. A few studies have suggested that MDA-modified proteins may exist in systemic diseases, and that autoantibodies to MDA-modified structures might reflect this oxidative process. Autoantibodies to MDA-modified epitope(s) were therefore assayed in sera of patients with systemic lupus erythematosus (SLE, n = 29), scleroderma (SCL, n = 11), giant cell arteritis (GCA, n = 11), periarteritis nodosa (PAN, n = 10), rheumatoid arthritis (RA, n = 9), and healthy subjects (HS, n = 32). Significantly increased anti-MDA-modified epitope(s) autoantibodies were found in patients with SLE and also in other systemic diseases such as PAN and SCL. Autoantibodies to MDA-modified epitope(s) were predominantly of IgM isotype, with low levels of IgG and no IgA activity. In SLE, anti-MDA-modified epitope(s) autoantibody titres 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 regimen (r = 0.52, P = 0.004). Autoantibodies to MDA-modified epitope(s) may reflect oxidative modifications occurring in systemic diseases, and might be useful as clinical markers of SLE activity if further investigated.
Amara
A
A
Laboratoire d'Immunologie, Université de Bordeaux II, France.
Constans
J
J
Chaugier
C
C
Sebban
A
A
Dubourg
L
L
Peuchant
E
E
Pellegrin
J L
JL
Leng
B
B
Conri
C
C
Geffard
M
M
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D003240:Connective Tissue Diseases / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000276:immunology*; D008875:Middle Aged; D014657:Vasculitis / Q000097:blood / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D007075:Immunoglobulin M; D008315:Malondialdehyde