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Objective To compare the cumulative survival and event free survival in patients with Jo-1 versus non-Jo-1 anti-tRNA synthetase autoantibodies (anti-synAb). Methods Anti-synAb positive patients initially evaluated from 1985 to 2009 were included regardless of the connective tissue disease (CTD) diagnosis. Clinical data were extracted from a prospectively collected database and chart review. Survival between Jo-1 and non-Jo-1 was compared by log rank and Cox proportional hazards methods. Results 202 patients possessed anti-synAb: 122 Jo-1 and 80 non-Jo-1 (35 PL-12; 25 PL-7; 9 EJ; 6 KS; 5 OJ). The diagnoses at first visit for Jo-1 and non-Jo-1 patients were myositis in 83% and 40.0%, overlap or undifferentiated CTD in 17% and 47.5%, and systemic sclerosis in 0% and 12.5%, respectively (p<0.001). The median delay in diagnosis was 0.4 years in Jo-1 patients versus 1.0 year in non-Jo-1 patients (p<0.001). The most common causes of death in the overall cohort were pulmonary fibrosis in 49% and pulmonary hypertension in 11%. The 5- and 10-year unadjusted cumulative survival was 90% and 70% for Jo-1 patients, and 75% and 47% for non-Jo-1 patients ( p<0.005). The hazard ratio (HR) of non-Jo-1 patients compared with Jo-1 patients was 1.9 (p=0.01) for cumulative and 1.9 (p=0.008) for event free survival from diagnosis. Age at first diagnosis and diagnosis delay but not gender, ethnicity and CTD diagnosis influenced survival. Conclusions Non-Jo-1 anti-synAb positive patients have decreased survival compared with Jo-1 patients. The difference in survival may be partly attributable to a delay in diagnosis in the non-Jo-1 patients.

Objective. To determine the long-term outcome and associated clinical, serologic, and pathologic features in a cohort of patients with connective tissue disease (CTD) and the anti-signal recognition particle (anti-SRP) autoantibody.Methods. Sera and clinical data were collected prospectively from consecutive adult patients with polymyositis (PM; n ‫؍‬ Conclusion. The anti-SRP autoantibody is not specific for PM. Severe muscle weakness and atrophy were prominent features in PM patients with anti-SRP.

Objective Epidemiology studies suggest that Systemic Sclerosis is more common, occurs at a younger age and is more severe in African-Americans than Caucasians. However, the scleroderma autoantibody profile is very different between these two ethnic subgroups. This study examines the demographic and disease features, frequency and severity of internal organ system involvement and survival in African-American and Caucasian SSc patients with particular attention to their serum autoantibody profiles. Methods Demographic, clinical, autoantibody, natural history of organ involvement and survival were studied in consecutive African-American and Caucasian patients seen between 1972 and 2007 as part of the Pittsburgh Scleroderma Database. The Medsger Disease Severity Scale was used to determine severe disease. Results African-American patients were more likely to have anti topoisomerase, anti U1RNP and U3 RNP auto-antibodies. Comparing African-American and Caucasians with these antibodies, African-American patients with anti topoisomerase antibody had more frequent and more severe pulmonary fibrosis than Caucasians and an associated decreased survival. Pulmonary fibrosis was also more severe in the U1 RNP patients but was not associated with a difference in survival between African Americans and Caucasians. Anti U3 RNP was associated with more severe gastrointestinal involvement in African-American’s compared to Caucasians. Conclusions African Americans with systemic sclerosis have more severe disease complications than Caucasians both because of the type of autoantibody they have and because they have more severe interstitial lung disease even within the antibody subset. Early aggressive intervention in all African Americans with interstitial lung disease should be a priority.

Objective To examine the association of skin thickness progression rate (STPR) with mortality, and as a predictor of future internal organ involvement in an inception cohort of diffuse cutaneous systemic sclerosis (SSc) patients. Methods Diffuse cutaneous SSc patients older than 16 years of age evaluated at the University of Pittsburgh within 2 years of the first evidence of skin thickening between 1980 and 2005 were eligible. The authors calculated the STPR on these patients, and examined the relationship of this variable to the development of early internal organ involvement and short-term mortality using logistic regression. Results 826 patients were included in the analysis. Patients with a rapid STPR experienced significantly reduced short-term survival at 1 and 2 years from the time of first Pittsburgh evaluation (p=0.002). Patients with a rapid STPR were more likely to develop renal crisis within 1–2 years of follow-up. Rapid STPR was found to be an independent predictor of both mortality (OR 1.72; 95% CI 1.13 to 2.62; p=0.01) and ‘renal crisis’ (OR 2.05, 95% CI 1.10 to 3.85; p=0.02) within 2 years from first evaluation. Conclusion The STPR is an easy measure to perform at the time of initial evaluation for identifying those diffuse cutaneous SSc patients who are at increased risk of mortality and the development of renal crisis during the following 2 years.

Systemic sclerosis sine scleroderma should be included in the spectrum of SSc with limited cutaneous involvement and should not be considered a distinct or separate disorder.

Objective. Previous case series have examined the relationship between anti-Jo-1 antibody levels and myositis disease activity, demonstrating equivocal results. Using enzyme-linked immunosorbent assays (ELISAs) and novel measures of myositis disease activity, the current study was undertaken to systematically reexamine the association between anti-Jo-1 antibody levels and various disease manifestations of myositis.Methods. Serum anti-Jo-1 antibody levels were quantified using 2 independent ELISA methods, while disease activity was retrospectively graded using the Myositis Disease Activity Assessment Tool, which measures disease activity in 7 different organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (VAS) and the Myositis Intention-to-Treat Index (MITAX) components. Spearman's rank correlation coefficients and mixed linear regression analysis were used to identify associations between anti-Jo-1 antibody levels and organ-specific disease activity in crosssectional and longitudinal analyses, respectively.Results. Cross-sectional assessment of 81 patients with anti-Jo-1 antibody revealed a modest correlation between the anti-Jo-1 antibody level and the serum creatine kinase (CK) level, as well as muscle and joint disease activity. Correlation coefficients were similar for CK levels (r s ‫؍‬ 0.38, P ‫؍‬ 0.002), myositis VAS (r s ‫؍‬ 0.36, P ‫؍‬ 0.002), and arthritis VAS (r s ‫؍‬ 0.40, P ‫؍‬ 0.001). In multiple regression analyses of 11 patients with serial samples, anti-Jo-1 antibody levels correlated significantly with CK levels (R 2 ‫؍‬ 0.65, P ‫؍‬ 0.0002), myositis VAS (R 2 ‫؍‬ 0.53, P ‫؍‬ 0.0008), arthritis VAS (R 2 ‫؍‬ 0.53, P ‫؍‬ 0.006), pulmonary VAS (R 2 ‫؍‬ 0.69, P ‫؍‬ 0.005), global VAS (R 2 ‫؍‬ 0.63, P ‫؍‬ 0.002), and global MITAX (R 2 ‫؍‬ 0.64, P ‫؍‬ 0.0003).Conclusion. In this large series of patients with idiopathic inflammatory myopathy, anti-Jo-1 antibody levels correlated modestly with muscle and joint disease, an association confirmed by a custom ELISA using recombinant human Jo-1. More striking associations emerged in a smaller longitudinal subset of patients that link anti-Jo-1 antibody levels to muscle, joint, lung, and global disease activity.

Objective. To assess the efficacy of tacrolimus in patients with anti-aminoacyl-transfer RNA synthetase (anti-aaRS)-associated interstitial lung disease (ILD) and idiopathic inflammatory myopathy (IIM).Methods. Ninety-eight patients with anti-aaRS autoantibodies were identified in our IIM cohort of 536 patients. The medical records of 15 patients with antiaaRS-associated ILD treated with tacrolimus between 1992 and 2003 were retrospectively reviewed. Pulmonary parameters of response included forced vital capacity, forced expiratory volume in 1 second, and diffusing capacity for carbon monoxide. Manual muscle testing results, serum creatine kinase (CK) levels, and the daily corticosteroid dosage were used to assess improvement in myositis. Random coefficient modeling considering polynomials of time was used to assess the clinical response to tacrolimus.Results. All patients, except for 1, who had pure ILD, had definite or probable IIM. Two patients received tacrolimus for fewer than 3 months, and their data were not analyzed. For the remaining 13 patients, the mean age at onset of ILD was 46.9 years, and the mean duration of pulmonary disease was 14.7 months. Twelve patients had anti-histidyl-transfer RNA synthetase autoantibody (anti-Jo-1) and 1 had anti-alanyltransfer RNA synthetase autoantibody (anti-PL-12). Patients received tacrolimus for an average of 51.2 months. A significant improvement was observed in all pulmonary parameters measured. The serum CK level declined significantly, and 10 patients had either an improvement in muscle strength or maintained normal muscle strength. A statistically significant reduction in the corticosteroid dosage was also observed. Conclusion. Tacrolimus is a well-tolerated and effective therapy for managing refractory ILD and myositis in anti-aaRS-positive patients.The idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous disorders characterized by skeletal muscle weakness and the presence of inflammatory infiltrates on muscle biopsy. The most common autoantibody in IIM targets the anti-aminoacyltransfer RNA synthetase (anti-aaRS) specific for histidine (anti-Jo-1); other antibodies are directed against the aaRS for threonine (PL-7), alanine (PL-12), glycine (EJ), asparagine (KS), and isoleucine (OJ). The "antisynthetase syndrome," which is seen in many patients with anti-aaRS autoantibodies, is characterized by myositis, fever, ILD, inflammatory arthritis, and Raynaud's phenomenon.ILD is a frequent manifestation of polymyositis (PM) and dermatomyositis (DM), and in patients with antisynthetase autoantibodies, the prevalence has been reported to exceed 50% (1-9). Corticosteroids remain the empirical first-line therapy for myositis-associated ILD, but additional immunosuppressive agents are often necessary, including azathioprine, cyclophosphamide, cyclosporine, and tacrolimus. In a previous pilot trial, tacrolimus, a relatively specific inhibitor of lymphocyte proliferation, showed promise in patients with refractory myositis and ILD who were positive for an...