Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis.
Systemic sclerosis (SSc) is characterized by multi-organ fibrosis with an autoimmune background. Although autoantibodies are detected frequently in SSc patients, the role of autoantibody in the development of fibrosis remains unknown. Connective tissue homeostasis is a balance between the synthesis and degradation of the extracellular matrix (ECM); ECM degradation is regulated mainly by matrix metalloproteinases (MMPs). Anti-MMP-1 antibody is suggested to inhibit MMP-1 and be involved in the development of the fibrosis in SSc. However, the accumulation of various ECM components in the tissue of SSc cannot be explained by the anti-MMP-1 antibody alone. In this study, we examined the presence or levels of antibody to MMP-3, a protein which degrades various ECM components relevant to SSc fibrosis. Enzyme-linked immunosorbent assay (ELISA) using human recombinant MMP-3 revealed that IgG anti-MMP-3 autoantibody levels were elevated significantly in the sera from SSc patients, but not in patients with active systemic lupus erythematosus or dermatomyositis. IgG and IgM anti-MMP-3 antibody levels were significantly higher in diffuse cutaneous SSc, a severe form, than those in limited cutaneous SSc. Consistently, IgG anti-MMP-3 antibody levels correlated significantly with fibrosis of the skin, lung and renal blood vessels. The presence of IgG anti-MMP-3 autoantibody in sera from SSc patients was confirmed by immunoblotting analysis. Remarkably, MMP-3 activity was inhibited by IgG anti-MMP-3 antibody. These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM turnover.
Nishijima
C
C
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Hayakawa
I
I
Matsushita
T
T
Komura
K
K
Hasegawa
M
M
Takehara
K
K
Sato
S
S
D001323:Autoantibodies / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D003882:Dermatomyositis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005109:Extracellular Matrix / Q000276:immunology; D005260:Female; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D008168:Lung / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000097:blood / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*; D012867:Skin / Q000473:pathology
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019278:Matrix Metalloproteinase 3