Background Systemic sclerosis (SSc) is a connective tissue disorder with excessive fibrosis of the skin and various internal organs. Although SSc is a heterogeneous disease, it has been reported that the particular antinuclear antibodies (ANA) are often indicative of clinical features, disease course and overall severity. Objective To clarify the association of clinical and prognostic features with serum ANA in Japanese patients with SSc. Methods We studied 203 Japanese patients diagnosed with SSc, who visited our hospital during the period 1983–2005. Six SSc-related ANA were identified using indirect immunofluorescence, double immunodiffusion and immunoprecipitation assays. Results Patients with SSc were classified into six ANA-based subgroups and a group without ANA. As expected, antitopoisomerase I antibody (Ab, n = 64), anti-RNA polymerases (RNAP) Ab ( n = 12) and anti-U3 RNP Ab ( n = 5) were associated with diffuse cutaneous SSc, whereas anticentromere Ab (ACA, n = 75), anti-Th/To Ab ( n = 7) and anti-U1 RNP Ab ( n = 10) were frequently detected in patients with limited cutaneous SSc. Clinical features of the ANA-negative group ( n = 10) were heterogeneous. Consistent with previous findings in Caucasian and/or black African patients, antitopoisomerase I Ab was associated with the involvement of vascular and pulmonary fibrosis, leading to decreased survival rate. However, no patients with anti-RNAP Ab developed renal crisis and the frequency of isolated pulmonary hypertension in patients with ACA, anti-Th/To Ab or anti-U3 RNP Ab was similar to that in other ANA-based subgroups. Conclusion These results indicate that the clinical relevance of SSc-related ANA in Japanese patients differs in some aspects from that in Caucasian and/or black African patients.

SUMMARY 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.

Background: Serum KL-6 has been suggested to be a useful marker for the evaluation of interstitial lung disease activity. Objective: To determine the correlation between serum KL-6 levels and pulmonary fibrosis in patients with systemic sclerosis (SSc). Methods: Serum samples from patients with limited cutaneous SSc (lSSc; n = 19), diffuse cutaneous SSc (dSSc; n = 26) and normal individuals (n = 15) were examined by ELISA. Results: Serum KL-6 levels in SSc patients were significantly higher than those in normal controls. KL-6 levels in dSSc patients were significantly elevated compared with those in lSSc patients. Elevated KL-6 levels were associated with the presence of pulmonary fibrosis in SSc patients or dSSc patients. Furthermore, KL-6 levels inversely correlated with percentages of diffusion capacity of carbon monoxide and vital capacity in SSc patients or dSSc patients. Conclusion: KL-6 may be a simple, serologic indicator for the severity of pulmonary fibrosis in SSc.

Although renal crisis is rare in Japanese SSc patients, our study suggests that latent and subclinical renal damage exists in these patients.

A 54-year-old Japanese man without apparent immunosuppression presented with nodules with purulent drainage on the right lower leg. He had ringworm of the right leg and tinea unguium. A biopsy specimen of the nodule showed intradermal abscesses with fungal elements, and Trichophyton rubrum was cultured from both the pus and the biopsy specimen. Treatment with oral terbinafine resolved the nodules. Dermatophyte abscess is a rare, deep and invasive dermatophytosis, which is often associated with immunocompromised conditions. We provide a review of the literature including Japanese cases.