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OBJECTIVE: Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. METHODS: Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. RESULTS: Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded > 12 weeks following the reported infection. Respondents were 91.6% female, 91.2% White, median (IQR) age was 48 (40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). Eighty-nine of 299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an effect on QOL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2 [2-3] vs 3 [2-3]; P < 0.001) and more reinfections (16.9% vs 5.7%; P = 0.004). CONCLUSION: In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections.

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The coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in increased morbidity and mortality in patients with impaired immunity, hematologic malignancies, and immunosuppressive regimens. COVID-19 can cause a cytokine storm with some patients benefiting from blockade of the pro-inflammatory cytokine, interleukin 6 (IL6). As Castleman disease (CD) is an atypical lymphoproliferative disorder that can involve a cytokine storm and often requires immunosuppressive therapies, including IL6 inhibition, we sought to evaluate outcomes following COVID-19 and SARS-CoV-2 vaccination in CD patients. We administered a survey in April 2021 to characterize experiences with COVID-19 and SARS-CoV-2 vaccination among 300 CD patients enrolled in ACCELERATE, a natural history registry of CD patients. Among 128 respondents, the prevalence of SARS-CoV-2 infection (16/95, 17%), severe disease (1/16, 6%), vaccination rates (112/128, 88%), and vaccine adverse effects after dose one (62/112, 55%) were comparable to the general U.S. population. While there were two cases of CD flares occurring shortly after SARS-CoV-2 infection (N=1) and vaccination (N=1), over 100 patients in this study that were infected and/or vaccinated did not experience CD flares. The median anti-spike titer six months after the second dose among CD patients was comparable to individuals with other immune-related diseases and healthy populations. Data from this small cohort suggest that, despite being on immunosuppressive therapies, CD patients do not appear to be at increased risk of poor COVID-19 outcomes and can mount a humoral response to SARS-CoV-2 vaccination. This study was registered on clinicaltrials.gov (#NCT02817997).

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Idiopathic inflammatory myopathies are a group of autoimmune diseases with a broad spectrum of clinical presentations, primarily characterised by immune-mediated muscle injury. Until recently, there was little insight into the pathogenesis of idiopathic inflammatory myopathies, which challenged the recognition of the breadth of heterogeneity of this group of diseases as well as the development of new therapeutics. However, the landscape of idiopathic inflammatory myopathies is evolving. In the past decade, advances in diagnostic tools have facilitated an enhanced understanding of the underlying disease mechanisms in idiopathic inflammatory myopathies, enabling the expansion of therapeutic trials. The fields of transcriptomics, prot§eomics, and machine learning offer the potential to gain greater insights into the underlying pathophysiology of idiopathic inflammatory myopathies. Harnessing insights gained from these sophisticated tools could contribute to the identification of differences at a molecular level among patients, accelerating the development of targeted, tailored therapies. Bolstered by the validation and standardisation of robust outcome measures, many promising therapies are in clinical trial development. Although challenges remain, there is great optimism in the field due to the progress in innovative diagnostics, outcome measures, and therapeutic approaches. In this Review, we discuss the expanding landscape of idiopathic inflammatory myopathies as the frontier of precision medicine becomes imminent.

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Patients with inflammatory arthritis (IA) are at increased risk of severe COVID-19 due to medication-induced immunosuppression that impairs host defenses. The aim of this study was to assess antibody and B cell responses to COVID-19 mRNA vaccination in IA patients receiving immunomodulatory therapies. Adults with IA were enrolled through the Johns Hopkins Arthritis Center and compared with healthy controls (HC). Paired plasma and peripheral blood mononuclear cell (PBMC) samples were collected prior to and 30 days or 6 months following the first two doses of mRNA vaccines (D2; HC=77 and IA=31 patients), or 30 days following a third dose of mRNA vaccines (D3; HC=11 and IA=96 patients). Neutralizing antibody titers, total binding antibody titers, and B cell responses to vaccine and Omicron variants were analyzed. Anti-Spike (S) IgG and S-specific B cells developed appropriately in most IA patients following D3, with reduced responses to Omicron variants, and negligible effects of medication type or drug withholding. Neutralizing antibody responses were lower compared to healthy controls after both D2 and D3, with a small number of individuals demonstrating persistently undetectable neutralizing antibody levels. Most IA patients respond as well to mRNA COVID-19 vaccines as immunocompetent individuals by the third dose, with no evidence of improved responses following medication withholding. These data suggest that IA-associated immune impairment may not hinder immunity to COVID-19 mRNA vaccines in most individuals.

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PURPOSE OF REVIEW: Systemic sclerosis associated myopathy (SSc-AM) is a complex, heterogenous disease that is associated with poor outcomes. SSc-AM lacks a clear definition, and continues to be poorly recognized. The purpose of this review is to provide a contemporary overview of the clinical, serological and pathophysiologic findings in SSc-AM to guide optimal recognition and management of this challenging disease manifestation. RECENT FINDINGS: There have been several advances in diagnostic techniques to facilitate characterization of SSc-AM, including muscle MRI, in which findings were correlated to distinct histopathologic categories of muscle involvement in SSc, histopathologic findings of prominent fibrosis or inflammation on biopsy, and the identification of novel autoantibodies associated with SSc-AM, which may be associated with distinct clinical phenotypes. In one of the largest studies to date, 17% of a well phenotyped SSc cohort were found to have myopathy, which was an independent risk of death, even after adjusting for potential confounders, further highlighting the importance of timely recognistion and management of SSc-AM. SUMMARY: There is increasing recognition of the importance of SSc-AM. Novel diagnostic tools provide the opportunity for more detailed insights into pathophysiologic mechanisms, which may facilitate the development of a rigorous consensus definition of SSc-AM.

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Background: The emergence of new SARS-CoV-2 variants calls for more data on SARS-CoV-2 mRNA vaccine response. Aims: We aimed to assess the response to a third mRNA vaccine dose against SARS-CoV-2 in inflammatory bowel disease (IBD) patients. Methods: This was a single-center, observational prospective study of IBD patients who received a third mRNA vaccine dose against SARS-CoV-2. Antibody titers were taken post-third-dose at one and three months using the Roche Elecsys anti-SARS-CoV-2-S enzyme immunoassay. Titers less than 0.8 units/mL were considered negative according to the manufactures. Titers between 0.8 units/mL and 250 units/mL were considered non-neutralizing. Titers greater than 250 units/mL were considered neutralizing. Results: Eighty-three patients were included, all of whom had detectable antibodies at 3 months post-third dose. A total of 89% showed neutralizing and 11% non-neutralizing titers. Participants with non-neutralizing titers were more likely to be on systemic corticosteroids (p = 0.04). Two participants seroconverted from negative to positive, whereas 86% with non-neutralizing titers boosted to neutralizing levels. Only one participant with neutralizing titers after a third dose had a decrease to a non-neutralizing level within 3 months. Conclusions: Our findings support the ongoing recommendations for additional doses in immunocompromised individuals. However, longitudinal studies with a greater-sized patient population are needed.

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INTRODUCTION: Idiopathic inflammatory myopathies (IIMs) represent a diverse group of systemic autoimmune disorders with variable clinical manifestations and disease course. Currently, the challenges of IIMs are multifold, including difficulties in timely diagnosis owing to clinical heterogeneity, limited insights into disease pathogenesis, as well as a restricted number of available therapies. However, advances utilizing myositis-specific autoantibodies have facilitated the definition of subgroups as well as the prediction of clinical phenotypes, disease course, and response to treatment. AREAS COVERED: Herein we provide an overview of the clinical presentations of dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, and inclusion body myositis. We then provide an updated review of available and promising therapies for each of these disease groups. We synthesize current treatment recommendations in the context of case-based construct to facilitate application to patient care. Finally, we provide high-yield, clinical pearls relevant to each of the subgroups that can be incorporated into clinical reasoning. EXPERT OPINION: There are many exciting developments on the horizon for IIM. As insights into pathogenesis evolve, the therapeutic armamentarium is expanding with many novel therapies in development, holding promise for more targeted treatment approaches.

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Idiopathic inflammatory myopathies (IIMs) represent a heterogeneous group of systemic autoimmune diseases characterized by immune-mediated muscle injury. As insights into pathogenesis of IIM evolve, novel therapeutic strategies have become available to optimize outcomes. Herein, we summarize novel and emerging strategies in the management of dermatomyositis (DM), immunemediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM).

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OBJECTIVE: Proteinuria is the clinical expression of lupus nephritis and despite recent advances in the therapeutic armamentarium for lupus nephritis, morbidity and mortality rates remain high. Therefore, the identification of factors that predict lupus nephritis is paramount in preventing damage accrual and disease progression. Lipoprotein (a) (Lp[a]) is a primarily genetically inherited plasma lipoprotein with pro-thrombotic and pro-atherosclerotic effects. Elevated Lp(a) has been observed at early stages of renal impairment in the general population and is associated with the development of chronic kidney disease. However, little is known about renal implications of Lp(a) in SLE. Thus, we evaluated Lp(a) and atherosclerotic events, thrombotic events, renal disease, and disease activity in patients with SLE. METHODS: SLE patients fulfilling the revised American College of Rheumatology (ACR) or SLICC classification criteria with a measurement of Lp(a) were included in the analysis. A cutoff of 125 nmol/L was chosen based on expert opinion. Chi-square test was used to compare the differences between patient characteristics and Lp(a) levels. Logistic regression or linear regression were used, where appropriate, to assess the association between Lp(a) values and the measured outcomes. RESULTS: Lp(a) levels from 562 patients were analyzed. There was an association between elevated Lp(a) and a history of proteinuria (OR 1.58, p-value = 0.02). This association remained significant following adjustment for age, sex, race, low C3, and elevated anti-dsDNA (OR = 1.55, p-value = 0.04). There was also an association with eGFR < 60 (p = 0.02). Patients with elevated Lp(a) had higher physician global activity (p = 0.01) and erythrocyte sediment rate (p = 0.03). CONCLUSION: Elevated Lp(a) was associated with proteinuria, independent of known factors associated with lupus proteinuria, as well as reduced eGFR and physician global activity. Our findings highlight the potential role of Lp(a) as a noninvasive biomarker for early renal disease in SLE.

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