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Objectives: Anti‐signal recognition particle (SRP) antibodies, markers of immune‐mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti‐SRP antibodies against the myocardium through in vivo and in vitro studies. Methods: Total immunoglobulin G (IgG), purified from patients with positive anti‐SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure–volume loop; cardiac histological changes were analysed using haematoxylin–eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments. Results: After the passive transfer of total IgG from patients with positive anti‐SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti‐SRP‐specific IgG, however, recovered normal mitochondrial metabolism after treatment with N‐acetylcysteine, an ROS scavenger. Moreover, patients positive for anti‐SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching. Conclusion: Anti‐SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti‐SRP antibody‐induced LVDD. [ABSTRACT FROM AUTHOR]

Objective Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder. The understanding of the changes in adaptive immune cells and the crosstalk between innate and adaptive immune systems in AOSD is limited. This study aimed to examine the peripheral immune cell composition and inflammatory protein levels in AOSD patients. Methods Twenty-nine active AOSD patients were enrolled. Flow cytometry was used to analyse the cell populations in peripheral blood. Antibody chips were utilized to detect the protein expression profile in serum. Results In active AOSD patients, there was an increase in the percentage of classical and non-classical monocytes among peripheral blood mononuclear cells. The proportion of natural killer (NK) cells decreased, with an increase in CD56dim NK1 cells and a decrease in CD56bright NK2 cells compared with healthy controls (HCs). The percentage of naïve central memory T cells was decreased, while the percentage of effector and effector memory T cells was increased among adaptive lymphocytes. The proportion of naïve B and memory B cells was decreased, while plasma cells were increased in AOSD patients, indicating activation of the adaptive immune system. Additionally, the serum levels of 40 proteins were elevated in AOSD patients, primarily involved in cytokine–cytokine receptor interaction, inflammatory response and regulation of mitogen-activated protein kinase cascade. Conclusion Our findings showed the activation of the innate and adaptive immune system in AOSD. The protein–protein interaction analysis suggested potential communication between innate and adaptive cell subsets. These findings provide new insights into the pathogenesis of the disease and the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have underlined the genetic susceptibility in the pathogenesis of palindromic rheumatism (PR), but the known PR loci only partially explain the disease's genetic background. We aimed to genetically identify PR by whole‐exome sequencing (WES). Methods: This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti–citrullinated protein antibody (ACPA−) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU/liter). We conducted whole‐exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA− PR and ACPA+ PR. Results: Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA−. We identified 8 novel loci (in the ACPA− PR group: ZNF503, RPS6KL1, HOMER3, HLA–DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA− PR group: HLA–DRB1*0803 and HLA–DQB1; in the ACPA+ PR group: HLA–DPA1*0401) that were associated with PR and that surpassed genome‐wide significance (P < 5 × 10−8). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R2 < 0.025), whereas ACPA+ PR and ACPA− PR showed a moderate genetic correlation (0.38 < R2 < 0.8). Conclusion: This study demonstrated the distinct genetic background between ACPA− and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar. [ABSTRACT FROM AUTHOR]

Objective A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. Methods We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBP-CorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period, and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. Results A total of 122 patients with inactive AOSD were included, of which 49.2% (n  = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% vs 6.8%), and no relapse occurred within 1 month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. Conclusion Increased disease activity or relapse following vaccination with inactivated SARS–CoV-2 was rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS–CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Objective To explore whether inactivated coronavirus disease 2019 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary APS patients. Methods We enrolled 39 primary APS patients who received two doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and 4 weeks after the second dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments. Results There was no significant difference in the presence of all 11 autoantibodies detected before and 4 weeks after vaccination: for aCL, IgG (14 vs 16, P  = 0.64), IgM (13 vs 19, P  = 0.34), IgA (2 vs 3, P  = 0.64); anti-β2GP1, IgG (12 vs 12, P  = 1.00), IgM (5 vs 8, P  = 0.36), IgA (4 vs 3, P  = 0.69); anti-PS/PT IgG (13 vs 16, P  = 0.48), IgM (17 vs 22, P  = 0.26); LAC (22 vs 28, P  = 0.16); aPF4-heparin (0 vs 0, P  = 1.00) and ANA (23 vs 26, P  = 0.48). Notably, the distribution of the aPL profile in the pre- and post-vaccination cohorts was not affected by SARS-CoV-2 vaccination: for patients with a low-risk aPL profile (11 vs 10, P  = 0.799) and patients with a high-risk aPL profile (28 vs 29, P  = 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination. Conclusion Inactivated SARS-CoV-2 vaccine does not influence the profile of anti-phospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies (aPL) and thrombotic or obstetric events. Given the heterogeneity of the clinical manifestations, it is likely that genetic and acquired factors are involved in the pathogenesis of APS. The inherited polymorphisms of the thrombophilic gene, including methylenetetrahydrofolate reductase (MTHFR) C677T, type 1 plasminogen activator inhibitor (PAI-1) 4G/5G, factor V Leiden (FVL) G1691A, prothrombin (PT) G20210A, antithrombin (AT), and fibrinogen (Fg) polymorphisms, were analyzed in 67 aPL(+) patients from the Chinese Han population, including 41 APS patients and 26 persistent aPL carriers. The MTHFR C677T genotypes of 105 healthy controls, and the PAI-1 4G/5G polymorphism of 120 healthy controls, from the Chinese Han population were acquired for this study. Both the MTHFR C677T genotype (χ2 = 10.67, p = 0.004) and C/T allele distribution (χ2 = 5.92, p = 0.019) between the aPL(+) patients and healthy controls were found to be significantly different. Furthermore, we observed that the patients with at least one T allele had a higher risk of arterial thrombosis (CT vs. CC, OR 11.00, p= 0.025; CT + TT vs. CC, OR 10.27, p = 0.018). The C677T mutation of MTHFR is a risk factor for arterial thrombosis in Chinese Han patients with APS. [ABSTRACT FROM AUTHOR]

Objectives To explore the efficacy of plasma exchange (PE) therapy in refractory idiopathic inflammatory myopathy (IIM) patients with positive anti-signal recognition particle (SRP) antibody. Methods Nine refractory IIM patients with positive anti-SRP antibody were enrolled, who received PE therapy at Ruijin Hospital from October 2017 to December 2020. The clinical manifestations, laboratory tests, chest CT and lower extremity MRI images before and after PE therapy were compared. The treatment response was evaluated by the 2016 ACR/EULAR myositis response criteria. Results A total of 88.9% (8/9) of subjects had achieved improvement by 3 weeks after PE therapy, with 55.6% (5/9) minimal improvement and 33.3% (3/9) moderate improvement. There were statistically significant improvements between baseline and after PE therapy at 3 weeks on the core set measures: physician global activity, patient global activity, HAQ, manual muscle testing (MMT), extramuscular disease activity, and muscle enzymes activity including creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), except for alanine transaminase (ALT). Moreover, the chest CT showed regression of ground glass opacities and irregular linear opacities after PE therapy in four patients with interstitial lung disease. The MRI images of lower extremity in four patients showed reduction of muscle oedema after the therapy. Conclusion PE therapy is effective for refractory IIM patients with positive anti-SRP antibody. It should be considered as an alternative treatment for those patients who are resistant to the combined therapy of glucocorticoids and immunosuppressive agents. [ABSTRACT FROM AUTHOR]

Objectives Thrombosis occurring in the central nervous system is common in APS patients, leading to neuropsychiatric symptoms. We investigated the prevalence of silent brain abnormalities on MRI in primary APS (PAPS) patients and aPL carriers and assessed the association between the vascular risk factors, aPL profile, clinical manifestations and MRI abnormalities. Methods We consecutively included 44 PAPS patients, 24 aPL carriers and 23 healthy controls with comparable age and gender in a single-centre, observational, cross-sectional study. None of the patients had a history of stroke, transient ischaemic attack, migraine, dementia, epilepsy or bipolar disorders. On cerebral MRI, we assessed the imaging features and location of abnormality. Multivariate analysis was performed to identify the risk factors contributing to the MRI abnormalities. Results A total of 38 (55.88%) patients had abnormal MRI findings, while only one healthy control showed some abnormalities. Lacunes were the most frequent MRI abnormality in the aPL-positive group [31/68 (45.59%)], which were followed by white matter hyperintensities [20/68 (29.41%)]. In the study population, age [odds ratio (OR) 1.086, P  = 0.016] and LA positivity (OR 5.191, P  = 0.002) were independent associated factors with brain MRI abnormalities. When analysed in only the aPL-positive group, age (OR 1.116, P  = 0.007), female gender (OR 7.519, P  = 0.025) and thrombocytopenia (OR 8.336, P  = 0.047) were the significant independent risk factors with abnormal MRI. Conclusions PAPS patients and aPL carriers showed a high prevalence of brain MRI abnormalities, indicating an increased cerebrovascular risk, which emphasized attention to silent cerebral lesions in persistently aPL-positive patients. [ABSTRACT FROM AUTHOR]