RGD Reference Report - Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis. - Rat Genome Database

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

Authors: Nishijima, C  Hayakawa, I  Matsushita, T  Komura, K  Hasegawa, M  Takehara, K  Sato, S 
Citation: Nishijima C, etal., Clin Exp Immunol. 2004 Nov;138(2):357-63.
RGD ID: 8693674
Pubmed: PMID:15498049   (View Abstract at PubMed)
PMCID: PMC1809204   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1365-2249.2004.02615.x   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
systemic scleroderma  IDA 8693674 RGD 
systemic scleroderma  ISOMMP3 (Homo sapiens)8693674; 8693674 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp3  (matrix metallopeptidase 3)

Genes (Mus musculus)
Mmp3  (matrix metallopeptidase 3)

Genes (Homo sapiens)
MMP3  (matrix metallopeptidase 3)


Additional Information