title: Prevalence of HSP47 antigen and autoantibodies to HSP47 in the sera of patients with mixed connective tissue disease.
abstract: The 47-kDa heat shock protein (HSP47) is an endoplasmic reticulum molecular chaperone that assists in the maturation of collagen molecules and whose expression is known to be upregulated in lesions of fibrotic diseases. We examined the levels of HSP47 protein and autoantibodies to HSP47 in the sera of patients with rheumatic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and mixed connective tissue disease (MCTD) by enzyme-linked immunosorbent assay and immunoblot analysis. Patients with idiopathic pulmonary fibrosis (IPF) were assessed as an example of non-autoimmune fibrotic disease. HSP47 antigen and autoantibody levels are significantly elevated in the sera of the rheumatic autoimmune disease patients, but not in the sera of the IPF patients. The sera of the MCTD patients showed particularly high levels of HSP47 antigen relative to healthy controls (1.99+/-0.22 vs 0.41+/-0.07 ng/ml). Autoantibodies to HSP47 were also in high levels in the sera of MCTD patients. These results suggest that simultaneous occurrence of systemic inflammation and upregulation of HSP47 caused leakage of HSP47 from fibrotic lesions into the peripheral blood, and the leaked antigen induced high titer of autoantibodies to HSP47. The high levels of HSP47 antigen and autoantibody may be useful blood markers of MCTD.
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yokota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubota
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Motoko
authors.initials: M
authors.lastname: Naitoh
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hirata
authors.forename: Seiji
authors.initials: S
authors.lastname: Minota
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujii
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003240:Connective Tissue Diseases / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D050883:HSC70 Heat-Shock Proteins; D050958:HSP47 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000097:blood / Q000276:immunology; D006360:Heat-Shock Proteins / Q000097:blood* / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000097:blood / Q000276:immunology; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D050883:HSC70 Heat-Shock Proteins; D050958:HSP47 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006360:Heat-Shock Proteins; C494660:SERPINH1 protein, human