High prevalence of primary biliary cirrhosis and disease-associated autoantibodies in Japanese patients with systemic sclerosis.

OBJECTIVE: To investigate the prevalence of primary biliary cirrhosis (PBC) and PBC-associated autoantibodies in Japanese systemic sclerosis (SSc) patients. METHODS: Clinical data from 225 Japanese SSc patients were retrospectively obtained. Serum samples from these patients were examined for PBC-associated autoantibodies, anti-mitochondrial M2 antibodies (AMA), anti-sp100 antibodies (anti-sp100), and anti-gp210 antibodies (anti-gp210) by enzyme-linked immunosorbent assay. RESULTS: Of 225 patients, 37 (16.4%) had AMA, 13 (5.8%) had anti-sp100, and 3 (1.3%) had anti-gp210. Three patients were positive for both AMA and anti-sp100, and 2 were positive for both AMA and anti-gp210. PBC was found in 22 (9.8%) patients positive for AMA with or without anti-sp100 or anti-gp210, but not in those with anti-sp100 or anti-gp210 without AMA. Furthermore, 13 patients lacking these three antibodies were diagnosed with or suspected of PBC by liver biopsy and/or their clinical manifestation. Multivariable analysis revealed that AMA and anti-centromere antibodies were independently associated with PBC in SSc patients, while anti-sp100 and anti-gp210 were not. CONCLUSIONS: This study has demonstrated even higher prevalence of both PBC-associated autoantibodies and PBC in the Japanese SSc population than in the Caucasian SSc population. AMA and anti-centromere antibodies are likely to indicate increasing risk of PBC in SSc patients.

Usefulness of anti-cyclic citrullinated peptide antibody and rheumatoid factor to detect rheumatoid arthritis in patients with systemic sclerosis.

OBJECTIVES: The purpose of this study was to determine the prevalence of anti-CCP antibodies (anti-CCP Abs) and to assess associations between the presence of anti-CCP Ab and arthritis or arthralgia in SSc patients. METHODS: Serum samples were obtained from 146 SSc patients. Anti-CCP Ab, anti-agalactosyl (AG) IgG Ab, IgM-RF, IgG-RF and MMP-3 were determined, respectively. RESULTS: The presence of anti-CCP Ab was found in 18/146 (12%) patients with SSc. Elevated levels of anti-AG IgG Abs, IgM- and IgG-RFs were observed in 50/146 (34%), 17/146 (12%) and 4/146 (3%), respectively. Serum anti-CCP Ab levels were significantly elevated in SSc-RA overlap patients compared with SSc patients with or without arthralgia (P < 0.05 or P < 0.001, respectively). Serum MMP-3 levels did not correlate with the presence of arthritis or arthralgia but were significantly associated with modified Rodnan total skin thickness score. In SSc-RA overlap patients, 10/11 (91%) patients were positive for two or more RA-related Abs. CONCLUSIONS: The serum titre of anti-CCP Ab is higher in SSc-RA overlap patients than in SSc patients with or without arthralgia. The finding of high titres of anti-CCP Abs and the elevated levels combinatory with other RA-related Abs may help to define the diagnosis of SSc-RA overlap. MMP-3 might be a better marker to assess skin involvement rather than joint involvement in SSc patients.

Anti-topoisomerase I antibody levels as serum markers of skin sclerosis in systemic sclerosis.

The aim of the present study was to clarify the clinical significance of anti-topoisomerase I antibody (Ab) levels in Japanese patients with systemic sclerosis (SSc). Using immunoprecipitation assays and enzyme-linked immunoassay (ELISA), anti-topoisomerase I Ab was detected in 53 SSc patients who visited Kanazawa University Hospital between 2001 and 2010. In these patients, the association between serum anti-topoisomerase I Ab levels measured with ELISA and clinical features were compared using univariate analysis and multiple regression analysis. There were significantly positive correlations between anti-topoisomerase I Ab levels and the modified Rodnan total skin thickness score (MRSS) and skin thickness progression rate, and a significantly negative correlation with disease duration. On the other hand, anti-topoisomerase I Ab levels were not significantly associated with other clinical features including lung involvement. In a longitudinal study, anti-topoisomerase I Ab levels were decreased significantly in patients that had decreased MRSS, but not in patients that had unchanged or increased MRSS. There was a significantly positive association between anti-topoisomerase I Ab levels and MRSS and a significantly negative association with disease duration by multiple regression analysis. Our findings suggest that serum levels of anti-topoisomerase I Ab reflect the severity of skin sclerosis in patients with SSc.

Elevated serum APRIL levels in patients with systemic sclerosis: distinct profiles of systemic sclerosis categorized by APRIL and BAFF.

OBJECTIVE: Elevated serum concentrations of B cell-activating factor belonging to the tumor necrosis factor family (BAFF) are found in systemic sclerosis (SSc) and are associated with the severity of skin sclerosis. We investigated serum levels of a proliferation-inducing ligand (APRIL), a close homolog to BAFF, and its clinical association in patients with SSc as well as its correlation with BAFF. METHODS: Serum APRIL levels from 74 patients with SSc, 25 patients with systemic lupus erythematosus, and 25 healthy subjects were examined by ELISA. Clinical and laboratory measures were compared between SSc patients with elevated serum APRIL levels and those with normal levels. We assessed correlation of serum APRIL and BAFF levels in patients with SSc. RESULTS: Serum APRIL levels were elevated in SSc patients compared to controls. SSc patients with elevated serum APRIL levels had significantly higher incidences of pulmonary fibrosis than those with normal levels. Serum APRIL levels did not correlate with serum BAFF levels in SSc patients, and there were distinct profiles of SSc categorized by serum APRIL and BAFF levels. High APRIL levels served as a marker for involvement of pulmonary fibrosis and high BAFF levels served as a marker for severe skin sclerosis. CONCLUSION: The results suggest that elevated serum APRIL and BAFF levels were differentially associated with disease severity in SSc.