Prevalence of HSP47 antigen and autoantibodies to HSP47 in the sera of patients with mixed connective tissue disease

Yokota, Shinichi; Kubota, Hiroshi; Matsuoka, Yoshikazu; Naitoh, Motoko; Hirata, Daisuke; Minota, Seiji; Takahashi, Hiroki; Fujii, Nobuhiro; Nagata, Kazuhiro

doi:10.1016/s0006-291x(03)00352-8

Cited by 43 publications

(35 citation statements)

References 30 publications

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“…Since we previously demonstrated that HSP47 expression was higher in the lungs of patients with UIP than in those of controls, it was assumed that serum levels of HSP47 in S-IPF patients also would be higher than control levels. However, Yokota (one of the authors of the present manuscript) et al previously reported that the serum levels of HSP47 did not differ significantly between patients with S-IPF and healthy controls (Yokota et al 2003), and, in fact, that finding was reproduced in the present study (data not shown). Although a precise mechanism for the elevation of serum HSP47 levels only in patients with AE-IPF and not in patients with S-IPF was not elucidated in this study, the following is hypothesized: (1) the present study demonstrated that HSP47 expression was higher in DAD than in UIP lung tissue.…”

Section: Discussionsupporting

confidence: 65%

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Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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Little is known about the pathophysiology of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules. Previous studies in experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces collagen production and diminishes fibrosis progression. In this study, serum HSP47 levels were evaluated to elucidate pathogenic differences involving HSP47 between AE-IPF and stable (S)-IPF. -013-0411-5 and lactate dehydrogenase (LDH) were measured. Immunohistochemical analysis of lung HSP47 expression was determined in biopsy and autopsy tissues diagnosed as diffuse alveolar damage (DAD) and usual interstitial pneumonia (UIP). Serum levels of HSP47 were significantly higher in AE-IPF than in S-IPF patients, whereas serum levels of KL-6, SP-A, and SP-D did not differ significantly. Receiver operating characteristic curves revealed that HSP47 was superior for discriminating AE-IPF and S-IPF. The cutoff for HSP47 resulting in the highest diagnostic accuracy was 559.4 pg/mL; sensitivity, specificity, and diagnostic accuracy were 100.0 %, 93.9 %, and 96.2 %, respectively. Immunohistochemical analysis revealed that pulmonary HSP47 expression was greater in DAD than UIP tissues. Serum HSP47 was significantly higher in AE-IPF than in S-IPF patients, suggesting that underlying fibrogenic mechanisms involving HSP47 differ in the two conditions.Cell Stress and Chaperones (2013) 18:581-590 DOI 10.1007/s12192

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Section: Discussionsupporting

confidence: 65%

“…Sandwich enzyme-linked immunosorbent assay for determining HSP47 concentration Sandwich enzyme-linked immunosorbent assay for determining HSP47 concentration was carried out as described previously (Yokota et al 2000(Yokota et al , 2003. Serum levels of HSP47 were measured in all enrolled patients.…”

Section: Study Populationmentioning

confidence: 99%

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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“…Although the mechanism of release from cancer cell remains to be clarified, cell death could be involved. Alternatively, a deletion of the ER retention signal or an overflow of HSP47 from the ER retention signal may cause a leakage of HSP47 to outside the cell (Yokota et al, 2003). Only very limited release was noted from cultured fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…Only very limited release was noted from cultured fibroblasts. Recently, highserum auto-antibodies to HSP47 or HSP47 itself have been reported under inflammatory conditions, such as interstitial pneumonia and mixed connective tissue disease (Yokota et al, 2003;Kakugawa et al, 2008). If HSP47 is released from cancers in patients with UC, its detection in serum would be helpful for the clinical detection of malignancy.…”

Section: Discussionmentioning

confidence: 99%

High expression of HSP47 in ulcerative colitis-associated carcinomas: proteomic approach

et al. 2009

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BACKGROUND: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, known to be associated with a markedly increased risk of colorectal carcinoma development. METHODS: Using proteomic analysis with two-dimensional gel electrophoresis and mass spectrometry, differentially expressed proteins were assessed between UC-associated cancer and sporadic colon cancer cell lines. Western blot and immunostaining were performed for confirming the expression. RESULTS: Heat-shock protein of 47 kDa (HSP47) was identified as one of the proteins expressed more highly in UC-associated cancer cell lines, and an immunohistochemical examination confirmed significantly higher levels of HSP47 in UC-associated colon cancers than in sporadic counterparts, the expression increasing with a progression of neoplastic lesions. Heat-shock protein of 47 kDa was further found to be coexpressed with type I collagen in the cytoplasm, and both HSP47 and type I collagen were released from cultured cells into the culture medium. CONCLUSION: These results suggest that overexpression of HSP47 is a unique characteristic of UC-associated carcinoma related to type I collagen synthesis, with possible clinical applications.

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“…The colligin-1 is shorter than colligin-2 by 39 amino acids, but the other parts of the two proteins have 97.3% amino acid homology. Autoantibodies to colligin-2 have been described in rheumatoid arthritis (16,17) and mixed connective tissue disease (38). In our ELISA, we detected the anti-colligin-1 autoantibodies in 2 (19%) of the 11 patients.…”

Section: Discussionmentioning

confidence: 66%

Proteomic Surveillance of Autoantigens in Relapsing Polychondritis

Tanaka

Nakamura

Matsui

et al. 2006

Microbiology and Immunology

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Relapsing polychondritis (RP) is a rare systemic autoimmune disease, characterized by bilateral auricular chondritis, polyarthritis, nasal chondritis, respiratory tract chondritis, and audiovestibular damage (14,22). Inflammation of external ears with tissue deformity leads to 'cauliflower' ears (14, 26). Inflammation of cartilage of the nasal septum sometimes results in a 'saddle-nose' appearance. Inflammation of tracheolaryngeal tracts produces obstruction of airways by collapse of tracheal rings and bronchi. Polyarthritis occurs in large and small joints in RP. However, the arthritis in RP is generally asymmetric, non-erosive, and sero-negative. These characteristics are different from those of rheumatoid arthritis (RA) (25). Based on the systemic inflammation of cartilage, autoimmunity to cartilagerelated components would be involved in the pathogenesis of RP. As cartilage-related autoantigens in RP, several proteins had been reported so far. They include type II collagen (5,8,23), type IX collagen (10), type XI collagen (35), and cartilage oligomeric matrix protein (13). Recently, matrillin-1, which is expressed mainly in the tracheal cartilage not in articular cartilage, Abstract: Relapsing polychondritis (RP) is a systemic inflammatory disease, in which autoimmunity to cartilage-related components is thought to be involved in its pathogenesis. However, the autoimmune profile in RP has not been studied fully. We therefore investigated autoantibodies/autoantigens in RP comprehensively, by 2-dimensional electrophoresis (2DE), subsequent western blotting (WB) and mass spectrometry, using cell-extracted proteins as the antigen source. As a result, we detected 15 autoantigens on 2DE-WB, and further identified five of them. On average, one RP serum recognized approximately 8 out of the 15 autoantigens. Frequencies of the autoantibodies to the 5 identified antigens of tubulin alpha ubiquitous/6, vimentin, alpha enolase, calreticulin, and colligin-1/-2 were 91%, 46%, 36%, 82%, and 36%, respectively. ELISA using recombinant proteins for them revealed that frequencies of the autoantibodies to tubulin alpha ubiquitous, vimentin, alpha enolase, calreticulin, and colligin-1 were 36%, 64%, 46%, 27%, and 18%, respectively. Our data demonstrated that the autoimmune reaction was not restricted to cartilagerelated components, rather a variety of autoimmune responses occurred in patients with RP, which may be involved in the pathophysiology of RP. In addition, the proteomic approach using cell-extracted proteins would be a powerful way to investigate autoantigens.

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Prevalence of HSP47 antigen and autoantibodies to HSP47 in the sera of patients with mixed connective tissue disease

Cited by 43 publications

References 30 publications

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

High expression of HSP47 in ulcerative colitis-associated carcinomas: proteomic approach

Proteomic Surveillance of Autoantigens in Relapsing Polychondritis

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