ABSTRACT
OBJECTIVE: To clarify the mortality rates, causes of death, and contributing clinical factors in Japanese patients with systemic sclerosis (SSc). METHODS: A cohort of 405 patients with SSc, who attended our institution during the period 1973 to 2008, was retrospectively analyzed until the end of 2009. Clinical data were obtained from medical records or autopsy reports. RESULTS: The 405 patients with SSc consisted of 310 (76.5%) survivors, 86 (21.2%) who died, and 9 who were lost to followup. Diffuse cutaneous SSc and involvement of organs other than the gastrointestinal tract were more frequent in patients who died, and were associated with a worse prognosis according to Kaplan-Meier analysis. Female sex, limited cutaneous SSc, anticentromere antibody (ACA), and overlap with Sjögren's syndrome (SS) were factors favoring a better prognosis, while overlap with myositis contributed to a poor prognosis. The overall 10-year survival rate was 88%. The patients with SSc had a significantly higher mortality than the general population (standardized mortality ratio 2.76), but the patients with ACA or overlapping SS did not. The most common causes of death were unknown ones including sudden death, followed by malignancy and infection. In patients with pulmonary arterial hypertension, sudden death was the most common cause of mortality. CONCLUSION: The overall mortality rate of patients with SSc was higher than that of the general population, probably because of poor prognostic factors including organ involvement. These factors should be carefully monitored during followup.
Subject(s)
Cause of Death , Scleroderma, Systemic/mortality , Scleroderma, Systemic/physiopathology , Adolescent , Adult , Aged , Autoantibodies/blood , Child , Child, Preschool , Cohort Studies , Comorbidity , Female , Humans , Japan/epidemiology , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Factors , Scleroderma, Systemic/ethnology , Sjogren's Syndrome/mortality , Survival Analysis , Young AdultABSTRACT
We examined the direct effects of IFN-alpha on the development of Th17 with a system using immobilized anti-CD3, which permits activation of CD4+ T cells in the complete absence of accessory cells. Highly purified CD4+ T cells obtained from healthy donors were stimulated with immobilized anti-CD3 with or without IFN-alpha. IFN-alpha suppressed the production of IL-17 of immobilized anti-CD3-stimulated CD4+ T cells in a dose-response manner. Accordingly, IFN-alpha inhibited IL-17 mRNA expression in immobilized anti-CD3-stimulated CD4+ T cells. IFN-alpha did not affect the production of TGF-beta or IL-6, but inhibited RORC mRNA expression of anti-CD3-stimulated CD4+ T cells. These results indicate that IFN-alpha suppresses IL-17 expression and Th17 differentiation through down-regulation of RORC mRNA expression. It is therefore suggested that these effects might play a role in the mode of action of IFN-alpha in the treatment of various inflammatory diseases.
