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Objective To investigate novel systemic sclerosis (SSc) autoantibodies in autoantibody-negative patients and establish clinical associations. Methods Serum samples and clinical data for 548 patients with SSc were collected. Routine serologic techniques were used to test the serum samples for known SSc autoantibodies, and samples with negative results were further investigated by radiolabeled-protein immunoprecipitation assay. Sera that immunoprecipitated a novel 30-kd band were analyzed by indirect immunofluorescence and immunoprecipitation, using depleted cell extracts to establish a common reactivity. Mass spectrometry was performed to identify the novel autoantigen, and the results were confirmed using commercial antibodies. Sera from 426 patients with other forms of connective tissue disease, 103 with rheumatoid arthritis, 114 with idiopathic interstitial lung disease (ILD), and 150 healthy subjects were serotyped as controls. Results A novel autoantigen with a molecular weight of ∼30 kd was recognized by 7 sera from patients with SSc, 6 of whom had ILD, and by no controls. Six of the patients had diffuse cutaneous involvement, and 4 had overlap features with other autoimmune diseases. Immunodepletion experiments indicated that all samples targeted the same autoantigen, and mass spectrometry identified the novel autoantigen as eukaryotic initiation factor 2B (eIF2B). Conclusion We report the identification of a novel autoantibody (anti-eIF2B) in a small number of patients with SSc (∼1%); this autoantibody is closely associated with diffuse cutaneous manifestations and the presence of ILD. [ABSTRACT FROM AUTHOR]

Objective Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis-specific autoantibodies (MSAs) have prognostic significance in juvenile DM. Methods Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow-up 4.9 years). Long-term treatment status (on or off medication over time) was modeled using generalized estimating equations. Results Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48-fold higher odds (95% confidence interval [95% CI] 1.12-1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10-fold higher odds (95% CI 1.01-1.21; P = 0.038). A protective effect was identified in patients with anti-Mi-2 autoantibodies, in whom the odds of remaining on treatment were 7.06-fold lower (95% CI 1.41-35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti-nuclear matrix protein 2 autoantibodies, anti-transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61-fold higher odds (95% CI 1.16-2.22; P = 0.004), and for the total biopsy score, 1.13-fold higher odds (95% CI 1.03-1.24; P = 0.013). Conclusion Histopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease. [ABSTRACT FROM AUTHOR]

Objective. Calcinosis is a major cause of morbidity in JDM and has previously been linked to anti-NXP2 autoantibodies, younger age at disease onset and more persistent disease activity. This study aimed to investigate the clinical associations of anti-NXP2 autoantibodies in patients with JDM stratified by age at disease onset.Methods. A total of 285 patients with samples and clinical data were recruited via the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-NXP2 was determined by both immunoprecipitation and ELISA. Logistic regression analysis was performed to assess the age-dependent relationship between anti-NXP2 and the development of calcinosis and disease activity measures.Results. We identified anti-NXP2 autoantibodies in 56 patients (20%). While in all patients younger age at disease onset was associated with an increased risk of calcinosis and this relationship was nearly linear, anti-NXP2 autoantibodies substantially increased the risk of calcinosis across all ages (P = 0.025) and were detectable prior to calcinosis development. Children with anti-NXP2 autoantibodies had a greater degree of weakness (median lowest ever Childhood Myositis Assessment Score 29.6 vs 42) and were less likely to be in remission at 2 years post-diagnosis. No difference in disease activity was seen 4 years post-diagnosis.Conclusion. Children diagnosed at a young age have a high risk of calcinosis regardless of autoantibody status. However, the presence of anti-NXP2 autoantibodies substantially increases the risk of calcinosis across all ages and is associated with disease severity. [ABSTRACT FROM PUBLISHER]