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Objective: To analyze the clinical features and outcomes of the patients with anti-glycyl tRNA synthetase (anti-EJ) syndrome in a large Chinese cohort., Methods: The medical records, imaging, and serologic data of patients with anti-EJ antibodies from the China-Japan Friendship Hospital database were retrospectively investigated. Anti-EJ antibodies were identified using immunoblot assay. Long-term follow-up was conducted., Results: Anti-EJ antibodies were present in 46 (19.7%) of the 234 patients with antisynthetase syndrome (ASS), preceded by anti-Jo-1 and anti-PL-7 antibodies. The mean age of disease onset was 51.2 ± 15.9 years, and 69.6% of these patients were female. The most prevalent clinical feature was interstitial lung disease (ILD) (96.7%), which was also the most common initial manifestation, followed by fever (60.9%), mechanic's hands (56.5%), muscle involvement (50%), and Raynaud phenomenon (8.7%). Ten (21.7%) patients developed rapidly progressive ILD (RP-ILD). Organizing pneumonia (OP) on high-resolution computed tomography (HRCT) scans (OR = 37.5, p = 0.006) and a higher C-reactive protein-to-albumin ratio (CAR) (OR = 28.3, p = 0.01) were independent risk factors for RP-ILD. Muscular pathological features were heterogeneous. Concomitant infection was noted in 63.0% of the patients during the disease course. Hypoalbuminemia (OR = 0.759, p = 0.002) was an independent risk factor for concomitant infection. Patients responded well to glucocorticoid therapy. The 5- and 10-year survival rates of the patients with anti-EJ were 97.8% and 88%, respectively., Conclusion: Anti-EJ syndrome was found to be a relatively common ASS subtype, with a favorable outcome. A notable proportion of the patients experienced RP-ILD, which was prone to OP on HRCT and a higher CAR, and needed aggressive management. Key Points • ILD was the most common initial manifestation of anti-glycyl tRNA synthetase syndrome. • RP-ILD was notable in anti-EJ positive patients. • Anti-EJ positive patients possessed a favorable long-term prognosis, but easily relapsed.

Objectives: The aim of this study is to analyze the prevalence of myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with polymyositis (PM) and dermatomyositis (DM)., Methods: Twelve subsets of MSAs including anti-Mi-2, anti-TIF1-γ, anti-MDA5, anti-NXP2, anti-SAE1, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-OJ, and anti-HMGCR antibodies were tested. Four hundred and ninety-seven PM/DM patients were enrolled. Clinical features and laboratory data were collected. The frequency of MSAs and the correlations with clinical phenotypes were calculated by SPSS 21.0., Results: MSAs were present in 65.4% in PM/DM patients. Anti-TIF1-γ (14.3%), anti-MDA5 (12.5%), and anti-Jo-1 (10.1%) were the three commonest MSAs. Anti-SAE1 (OR 14.877, 95% CI 1.427-155.074), anti-SRP (OR 4.339, 95% CI 1.529-12.312) and anti-TIF1-γ (OR 2.790, 95% CI 1.578-4.935) were associated with dysphagia. In contrast, anti-MDA5 (OR 0.356, 95% CI 0.148-0.856) might decrease the frequency of this manifestation. Interstitial lung disease (ILD) was observed more frequently in patients carrying anti-EJ (OR 14.202, 95% CI 1.696-118.902), anti-Jo-1 (OR 11.111, 95% CI 3.306-37.335), and anti-MDA5 (OR 3.109, 95% CI 1.578-6.128). On the contrary, anti-Mi-2 (OR 0.180, 95% CI 0.055-0.589), anti-TIF1-γ (OR 0.163, 95% CI 0.080-0.333), and anti-HMGCR (OR 0.058, 95% CI 0.007-0.451) were protective factors against developing ILD. Anti-TIF1-γ was an independent risk factor for cancer-associated myositis (OR 4.237, 95% CI 1.712-10.487)., Conclusions: PM/DM patients had high frequencies of MSAs. Several MSAs were independent factors in determining unique clinical phenotypes.

Objective: To investigate the associations between anti-nuclear matrix protein 2 (anti-NXP-2) autoantibody levels and disease activity as well as calcinosis severity in patients with idiopathic inflammatory myopathies (IIMs)., Methods: Serum levels of anti-NXP-2 autoantibodies were determined in 709 patients with IIMs and also serially measured in the patients' sera with an in-house enzyme-linked immunosorbent assay using MORC3 recombinant protein. Patients with anti-NXP-2 autoantibodies were divided into 2 subgroups: those with and those without calcinosis. Associations of anti-NXP-2 autoantibody levels with organ-specific disease activity (using 10-cm visual analog scale [VAS] scores), serum creatine kinase (CK) levels, and calcinosis severity were investigated in cross-sectional and longitudinal analyses., Results: A cross-sectional analysis of 56 IIM patients with anti-NXP-2 autoantibodies (38 without calcinosis and 18 with calcinosis) showed that in patients without calcinosis, the levels of anti-NXP-2 autoantibodies were positively correlated with the physician's global assessment of disease activity and muscle VAS scores and serum CK levels, whereas no such association was found in patients with calcinosis. Results of the longitudinal study revealed strong correlations of anti-NXP-2 antibody levels with the physician's global assessment and constitutional, cutaneous, gastrointestinal, and muscle VAS scores and serum CK levels in patients without calcinosis, but in patients with calcinosis, only a moderate correlation was observed between anti-NXP-2 antibody levels and the physician's global VAS and constitutional VAS scores. Of note, in patients without calcinosis, anti-NXP-2 autoantibodies were found to disappear during periods of clinical remission, but reappeared with disease relapse. No association between anti-NXP-2 antibody levels and the severity of calcinosis was observed., Conclusion: These findings indicate that anti-NXP-2 autoantibodies serve as a useful marker for disease activity in patients with IIMs, especially in the absence of calcinosis. The differential associations observed between anti-NXP-2 autoantibody levels and disease activity suggest that there may be a phenotypic difference between patients with and those without calcinosis., (© 2018, American College of Rheumatology.)

Background: Cancer is a significant complication contributing to increased mortality in idiopathic inflammatory myopathies (IIMs), and the association between IIMs and cancer has been extensively reported. Myositis-specific autoantibodies (MSAs) can help to stratify patients into more homogeneous groups and may be used as a biomarker for cancer-associated myositis. In this study, we aimed to systematically define the cancer-associated MSAs in IIMs., Methods: Serum from 627 patients with IIMs was tested for MSAs. The cancer risk with different MSAs was estimated by standardized incidence ratio (SIR). Paraneoplastic manifestation, such as the close temporal relationship between myositis onset and cancer diagnoses in patients with different MSAs, was also evaluated., Results: Compared with the general Chinese population, patients with IIMs and anti-transcriptional intermediary factor (TIF1)-γ antibodies (SIR = 17.28, 95% CI 11.94 to 24.14), anti-nuclear matrix protein (NXP2) antibodies (SIR = 8.14, 95% CI 1.63 to 23.86), or anti-SAE1 antibodies (SIR = 12.92, 95% CI 3.23 to 32.94), or who were MSAs-negative (SIR = 3.99, 95% CI 1.96 to 7.14) faced increased risk of cancer. There was no association between specific MSAs subtypes and certain types of cancer. Paraneoplastic manifestations were observed in the patients carrying anti-TIF1-γ, as well as other MSAs. There were no prognostic differences among the patients with cancer-associated myositis (CAM) from different MSAs subgroups. However, in comparison to those with cancer unrelated to myositis, CAM had a worse prognosis, with an age-adjusted and sex-adjusted Cox hazard ratio (HR) of 10.8 (95% CI 1.38-84.5, p = 0.02) for all-cause mortality., Conclusions: Our study demonstrates in what is, to our knowledge, the largest population examined to date, that anti-SAE1, and previously reported anti-TIF1-γ and anti-NXP2 antibodies, are all associated with an increased risk of cancer in patients with IIMs. Moreover, our data suggest that in some cases, anti-HMGCR, anti-Jo-1 and anti-PL-12 antibody production might also be driven by malignancy. This can aid in the etiologic research of paraneoplastic myositis and clinical management.

Objective: To compare the clinical characteristics and identify the longterm outcomes of Chinese patients with different antisynthetase antibodies., Methods: We investigated retrospectively 124 consecutive patients with antisynthetase syndrome. Medical records, laboratory results, and computed tomography images were obtained., Results: The antisynthetase antibodies we investigated were anti-Jo1 (n = 62), anti-PL7 (n = 31), anti-PL12 (n = 12), and anti-EJ (n = 19). The overall prevalence of interstitial lung disease (ILD) reached 94.4% among study patients. Eleven patients (8.9%) developed rapidly progressive ILD (RP-ILD). Eight patients (6.5%) experienced malignancy. RP-ILD was statistically more prevalent in patients with antisynthetase syndrome with anti-PL7 than those without anti-PL7 (p = 0.028). Anti-Ro52-positive patients with antisynthetase syndrome experienced higher frequency of RP-ILD than those without anti-Ro52 (p = 0.001). Further, anti-PL7-positive patients coexisting with anti-Ro52 exhibited more RP-ILD than those without anti-Ro52 (p = 0.001). Patients with antisynthetase syndrome with RP-ILD had a higher proportion of neutrophils in bronchoalveolar lavage fluid and serum ferritin than those without RP-ILD (p = 0.006 and p = 0.013, respectively). Although no differences were observed between the Kaplan-Meier curves of the 4 antisynthetase antibodies subgroups (p = 0.349), the survival rate of patients with anti-PL7 decreased more rapidly in the early stage of longterm followup compared with those with other antisynthetase antibodies. The presence of RP-ILD, malignancy, and elevated serum ferritin was identified to be associated with poor prognosis in patients with antisynthetase syndrome., Conclusion: Our study investigates the clinical phenotypes and outcomes of patients with antisynthetase syndrome with distinct antisynthetase antibodies and highlights the link between the anti-PL7 antibody and RP-ILD.

Objective: This study was undertaken to investigate the long‐term survival rates and prognostic factors in patients with idiopathic inflammatory myopathies (IIMs) based on myositis‐specific antibody (MSA) stratification. Methods: Exactly 628 patients with an IIM were included. Kaplan‐Meier survival curves, univariate, and multivariate Cox regression were used to analyze the outcomes and risk factors. Results: The cumulative 1‐, 5‐, and 10‐year survival rates for IIM patients overall were 91.4%, 82.8%, and 75.6%, respectively. The survival rate in the MSA subset was significantly different (P < 0.001). The 1‐ and 10‐year survival rates in the anti–melanoma differentiation–associated protein 5 (anti–MDA‐5)–positive subgroup were 79.5% and 58.5%, respectively, which were the lowest among all subgroups. The 10‐year survival rate of anti–signal recognition particle (anti‐SRP)–positive patients was the highest (96.4%). Independent risk factors that impacted the long‐term prognosis for IIM patients included rapidly progressive interstitial lung disease (RP‐ILD), malignancy, and elevated serum ferritin levels (hazard ratio [HR] 17.47, 20.36, and 9.15, respectively, P < 0.01), whereas disease duration was a protective factor (HR 0.27, P = 0.003). Among these subsets, the strongest independent risk factor for death in the anti–MDA‐5–positive subgroup was RP‐ILD (HR 3.4, P = 0.017). Malignancy was an independent risk factor in the anti–aminoacyl‐tRNA synthetase antibody–positive, anti–transcription intermediary factor 1γ–positive, and MSA‐negative subgroups (HR 46.69, 6.65, and 4.48, respectively; P < 0.001). RP‐ILD was also a risk factor in the prognosis of individuals in the MSA‐negative subgroup (HR 72.28, P < 0.001). Conclusion: Despite favorable overall survival in patients with IIM, the anti–MDA‐5–positive subgroup had the highest mortality rate among all MSA subgroups, highlighting the distinctive prognosis for patients with different MSAs. RP‐ILD and malignancy are the most common causes of death in IIM patients. [ABSTRACT FROM AUTHOR]

Objective: Heterogeneity exists among patients with myositis who have antinuclear matrix protein 2 (anti-NXP2) antibodies, although they usually present with severe muscle weakness. This study aimed to investigate the differences in phenotypes and prognoses among adult patients with myositis who have anti-NXP2 antibodies.Methods: Adult patients with myositis who have anti-NXP2 antibodies were enrolled from January 2010 to December 2019. Their clinical features and laboratory data were recorded retrospectively. We followed up on their survival status until June 30, 2020. A hierarchical cluster analysis, Kaplan-Meier curves, and classification and regression trees were used to analyze the data.Results: A total of 70 adult patients with myositis who have anti-NXP2 antibodies were enrolled. All patients experienced muscle weakness. A total of 11 patients did not present with rashes during disease progression, and 43 patients developed dysphagia. In total, 21 patients had interstitial lung disease (ILD), whereas no patients had rapidly progressive ILD. Hierarchical cluster analysis identified 2 clusters. Patients in cluster 1 were younger at disease onset, had a higher incidence of subcutaneous calcification, and had a lower incidence of V sign and shawl sign. Patients in cluster 2 had a higher frequency of ILD, accompanied by lower levels of lymphocytes and higher levels of serum ferritin. Moreover, patients in cluster 2 had worse prognoses.Conclusion: Patients with myositis who have anti-NXP2 antibodies may present with different phenotypes that are characterized by unique features and prognoses. [ABSTRACT FROM AUTHOR]

Aims: The serum concentrations of miRNAs, miR-23a-3p, miR-23b-3p, miR-146a-5p, miR-146b-5p, and miR-150-5p, were shown to be associated with the immune and inflammatory progressions. We assessed the expressions of these five miRNAs in association with clinical phenotypes and myositis-specific autoantibody-defined subgroups of dermatomyositis (DM).Methods: The present study included 49 patients with DM and 30 healthy controls. The serum concentrations of miR-23a-3p, miR-23b-3p, miR-146a-5p, miR-146b-5p, and miR-150-5p were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Associations between the serum concentrations of miRNAs and DM clinical immune phenotypes were examined as well.Results: The serum concentrations of miR-23b-3p, miR-146a-5p, and miR-150-5p were significantly downregulated in DM patients (P < 0.001, P < 0.001, and P = 0.002, respectively), while miR-146b-5p was remarkably upregulated in DM patients compared with healthy controls (P = 0.039). Similarly, the expressions of miR-23b-3p, miR-146a-5p, and miR-150-5p were significantly downregulated in the peripheral blood mononuclear cells (PBMCs) from DM patients. Further study indicated that the serum level of miR-23b-3p was significantly correlated with creatine kinase (CK) (r = -0.286, P = 0.046) and the serum level of miR-146a-5p was evidently correlated with C-reactive protein (CRP) (r = -0.358, P = 0.012). Significant correlations were also observed between the serum levels of miR-146b-5p and CRP (r = -0.347, P = 0.014) and the erythrocyte sedimentation rate (ESR) (r = -0.287, P = 0.046). In addition, the expression level of miR-146b-5p was upregulated in DM complicated by tumors compared with those without tumors (P = 0.001 and P < 0.001, respectively). Especially, miR-150-5p was significantly downregulated in DM patients with anti-MDA5 antibodies and anti-NXP2 antibodies compared with those without (P = 0.017 and P = 0.047, respectively). No significant differences were observed between the four serum microRNAs in patients with and without interstitial lung diseases (all P > 0.05).Conclusion: The results suggest an association between the four immune-related microRNAs and different clinical immune-phenotypes, and this association may regulate the complexity of disease processes through multipathways in DM patients. [ABSTRACT FROM AUTHOR]