Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis.

Abstract

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.

• Authors: C Nishijima, I Hayakawa, T Matsushita, K Komura, M Hasegawa, K Takehara, S Sato
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 138 Issue 2 Pg. 357-63 (Nov 2004) ISSN: 0009-9104 [Print] England
• PMID: 15498049 (Publication Type: Journal Article)

Chemical References

• Autoantibodies
• Immunoglobulin G
• Immunoglobulin M
• RNA, Messenger
• Recombinant Proteins
• Matrix Metalloproteinase 3

Topics

• Autoantibodies (immunology)
• Cross Reactions (immunology)
• Dermatomyositis (immunology)
• Enzyme-Linked Immunosorbent Assay (methods)
• Extracellular Matrix (immunology)
• Female
• Humans
• Immunoblotting (methods)
• Immunoglobulin G (blood)
• Immunoglobulin M (blood)
• Kidney (blood supply, pathology)
• Lung (pathology)
• Lupus Erythematosus, Systemic (immunology)
• Male
• Matrix Metalloproteinase 3 (blood, immunology)
• Middle Aged
• Polymerase Chain Reaction (methods)
• RNA, Messenger (analysis)
• Recombinant Proteins (blood, immunology)
• Scleroderma, Systemic (immunology)
• Skin (pathology)