Systemic Autoimmune Rheumatic Diseases Research Articles

Prevalence and Risk Factors of Postacute Sequelae of COVID-19 in Adults With Systemic Autoimmune Rheumatic Diseases.

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. 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. 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). 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.

Pharmacotherapy of autoimmune rheumatic diseases – from monoclonal antibodies to CAR T cells: 20 years later

Autoimmunity is a pathological process associated with a violation of immunological tolerance to normal structural components of the body (autoantigens), associated with the predominance of active (adaptive) immunity and manifested by hyperproduction of autoantibodies. Systemic autoimmune rheumatic diseases (SARDs) are among the most common and severe nosological forms of this pathology associated with autoimmunity. Problems of pharmacotherapy of SARDs are the subject of intensive research. At the beginning of the 21st century, more than 20 biologic agents were developed for the treatment of rheumatoid arthritis – monoclonal antibodies (mAbs) and recombinant proteins that control inflammation associated with the overproduction of “pro-inflammatory” cytokines, the use of which has dramatically improved the results of pharmacotherapy. However, much less research has been devoted to studying the possibilities of pharmacotherapy aimed at selective suppression of the “autoimmune” component of the pathogenesis of SADRs associated with uncontrolled activation of B cells and restoration of immunological tolerance to autoantigens. In the spectrum of drugs whose mechanism of action is associated with the suppression of pathological activation of B cells, the leading place is occupied by rituximab (RTM). It is noteworthy that 20 years ago (2004), a group of researchers led by prof. J.C. Edwards first demonstrated the effectiveness of RTM in patients with RA, which was soon successfully repositioned to treat a wide range of SARDs. A major achievement in the pharmacotherapy of SARDs is associated with the use of CAR (сhimeric antigen receptor) T cell therapy, developed for the treatment of refractory hematological tumors. The main component of CART-cells is a genetically engineered T-cell receptor that recognizes the target antigen without the participation of the major histocompatibility complex. Although limited, extremely impressive data regarding high remission rates have been obtained by adapting CD19 CART-cell therapy to treat patients with severe systemic lupus erythematosus (SLE) and other SARDs refractory to standard immunosuppressive medications. The article discusses the results of the use of CART-cell therapy in SLE and other SARDs and prospects for further research.

Comment on: Incidence and Risk Factors of Mental Illnesses Among Patients with Systemic Autoimmune Rheumatic Diseases: An 18-year population-based study: Reply.

Comment on: Incidence and Risk Factors of Mental Illnesses Among Patients with Systemic Autoimmune Rheumatic Diseases: An 18-year population-based study: Reply.

Epidemiology of systemic sclerosis in Quebec, Canada: a population-based study

Systemic sclerosis (SSc) is a systemic life-threatening autoimmune rheumatic disease. We aimed to assess the incidence, prevalence, mortality and spatiotemporal trends of SSc in Quebec, Canada with stratification by sex and age. SSc cases were identified from Quebec populational databases from 1989 to 2019. Negative Binomial (NB) Generalized Linear Models were used for age-standardized incidence rates (ASIR) analyses and NB random walk for prevalence and mortality. A Poisson Besag-York-Mollié regression model was used for spatial analysis. 8180 incident SSc cases were identified between 1996 and 2019 with an average age of 57.3±16.3 years. The overall ASIR was 4.14/100,000 person-years (95%, Confidence Interval (CI) 4.05-4.24) with a 4:1 female predominance. ASIR increased steadily over time with an Average Annual Percent Change (AAPC) of 3.94% (95% CI 3.49-4.38). While the highest incidence rates were in those aged 60-79 years old among females and >80 years old among males, the highest AAPC (∼10%) was seen in children. Standarized incidence ratios varied geographically between 0.52 to 1.64. The average prevalence was 28.96/100,000 persons (95% CI 28.72-29.20). The Standardized Mortality Ratio (SMR) decreased from 4.18 (95% CI 3.64-4.76) in 1996 to 2.69 (95% CI 2.42-2.98) in 2019. Females had a greater SMR until 2007 and males thereafter. The highest SMR was in children and young adults [31.2 (95% CI 8.39-79.82) in the 0-19-year age group]. We showed an increasing trend in SSc incidence and prevalence and a decline in SMR over a 25-year period in Quebec. An uneven geographic distribution of SSc incidence was demonstrated. National Scleroderma Foundation, Canadian Dermatology Foundation/Canadian Institutes of Health Research.

Comment on: Incidence and risk factors of mental illnesses among patients with systemic autoimmune rheumatic diseases: an 18-year population-based study

Comment on: Incidence and risk factors of mental illnesses among patients with systemic autoimmune rheumatic diseases: an 18-year population-based study

Type I Interferons in Systemic Autoimmune Rheumatic Diseases: Pathogenesis, Clinical Features and Treatment Options.

Type I interferon (IFN) pathway dysregulation plays a crucial role in the pathogenesis of several systemic autoimmune rheumatic diseases (SARDs), including systemic lupus erythematosus (SLE), Sjögren's disease (SjD), systemic sclerosis (SSc), dermatomyositis (DM) and rheumatoid arthritis (RA). Genetic and epigenetic alterations have been involved in dysregulated type I IFN responses in systemic autoimmune disorders. Aberrant type I IFN production and secretion have been associated with distinct clinical phenotypes, disease activity, and severity as well as differentiated treatment responses among SARDs. In this review, we provide an overview of the role of type I IFNs in systemic autoimmune diseases including SLE, RA, SjD, SSc, and DM focusing on pathophysiological, clinical, and therapeutical aspects.

Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment

ObjectiveTo review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide.Materials and methodsThe search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators.ResultsEighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered.ConclusionThe current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

MDA5-autoimmunity and interstitial pneumonitis contemporaneous with the COVID-19 pandemic (MIP-C)

BackgroundAnti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 senses single-stranded RNA and is a key pattern recognition receptor for the SARS-CoV-2 virus. MethodsThis is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018-December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak. ResultsSixty new anti-MDA5+, but not other MSAs surged between 2020-2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response. ConclusionsA distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.

Neuropsychiatric prodromes and symptom timings in relation to disease onset and/or flares in SLE: results from the mixed methods international INSPIRE study

Neuropsychiatric symptoms in SLE and other systemic autoimmune rheumatic diseases (SARDs) are challenging to diagnose, attribute and manage. We investigated the timings of onset of a broad range of neuropsychiatric (NP) symptoms in relation to timing of SLE onset. In addition, we explored whether NP symptoms may be a prodrome to SARD onset and to subsequent flares. We collected patient reports of the timing of their first episode of 29 NP symptoms relative to SLE non-NP symptom onset. Surveys (n=676 SLE patients and n=400 clinicians) and interviews (n=50 clinicians; and n=69 SARD patients, including 27 SLE patients) were completed from 2022 to 2023, and analysed using mixed methods. The majority of NP symptoms did not first present around the time of SLE onset, contrary to the prevailing view among many rheumatology participants and in the literature. For example, among patients who experienced hallucinations, 54% reported first presentation >1 year after disease onset. Patient interviews also revealed that a range of NP symptoms may be a prodrome to SLE/SARDs onset and later flares, including symptoms not represented in existing classification criteria. Evidence of a possible prodromal syndrome was elicited from those patients who experienced hallucinations. Of these, 61% (SLE) and 34% (other SARDs) reported increasingly disrupted dreaming sleep (usually nightmares) prior to their hallucinations. In-depth interviews revealed that progression of symptoms in flares showed a high degree of inter-patient variation, whilst symptom progression was often similar in individual patient's recurrent flares. Neuropsychiatric symptoms can first present at any stage in the SLE disease course. Attributional decisions should evaluate timings of NP symptoms in relation to timing of SLE/SARD symptom onset rather than time of diagnosis due to frequent diagnostic delays. Greater recognition of prodromal/early NP symptoms indicating impending SLE flares (and potentially other SARD flares) could enable quicker flare identification and treatment. The Lupus Trust.

The development of anticyclic citrullinated peptide (anti-CCP) antibody following severe COVID-19.

The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID-19). This study was conducted to clarify the occurrence of autoantibodies (AABs) associated with systemic autoimmune rheumatic diseases (SARDs) in hospitalized patients with a moderate, severe, and critical form of COVID-19. The serum samples obtained from 176 hospitalized COVID-19 patients were investigated in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID-19. Also, the serum samples collected from healthy subjects before the COVID-19 pandemic were used as controls (N = 176). The antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), cytoplasmic-anti neutrophil cytoplasmic antibody (c-ANCA), perinuclear ANCA (p-ANCA), antiphospholipid antibodies (aPLs), and anticyclic citrullinated peptide (anti-CCP) occurrence was evaluated using a solid-phase enzyme-linked immunosorbent assay (ELISA). The results showed that the occurrence of ANAs, anti-dsDNA, anti-CCP, c-ANCA, and p-ANCA was significantly higher in the COVID-19 patients compared to serum obtained from healthy subjects (p < .0001, p < .0001, p < .0001, p < .05, and p < .001, respectively). The positive number of anti-CCP tests increased significantly in severe COVID-19 compared to the moderate group (p < .01). Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases. To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti-CCP in a severe form of COVID-19.

Periconceptional Counselling in Women with Autoimmune Inflammatory Rheumatic Diseases.

Systemic autoimmune rheumatic diseases (SARDs) in pregnancy represent a complex challenge for both patients and healthcare providers. Timely preparation for pregnancy enables adequate disease control, thereby reducing the risk of disease flare and pregnancy complications. Interdisciplinary care starting from the pre-pregnancy period throughout pregnancy and during breastfeeding ensures better fetal and maternal outcomes. This review provides a comprehensive guide to pre-pregnancy counselling in SARDs, an overview of medication management strategies tailored to pregnancy, disease activity and pregnancy monitoring in patients, and the promotion of shared decision making between healthcare providers and patients. Guidelines from international organizations were selected to provide a basis for this review and guidance through the quintessential discussion points of care.

Association Between Wearable Device Use and Quality of Life in Patients With Idiopathic Inflammatory Myopathies and Primary Systemic Vasculitis.

Background Despite the increasing use of wearable devices worldwide, concise data on these instruments in patients with systemic autoimmune rheumatic diseases, including idiopathic inflammatory myopathies (IIM) and primary systemic vasculitis (PSV), are lacking. Objectives The aim of this study is to investigate the knowledge and use of wearable devices and to assess their impact on the general quality of life of patients with IIM and PSV. Moreover, we compared these characteristics between patients with IIM and PSV users and non-users of wearable devices. Methods This single-center, cross-sectional study was conducted between January 2023 and June 2023. We included adult patients with IIM and PSV and a control group (CTR) and evaluated their use of cell phones and wearables, level of physical activity, and quality of life. Results A total of 132 patients with IIM, 82 with PSV, and 178 in the CTR were evaluated. Overall, 169 patients and 144 in the CTR were aware of wearable devices, of whom 50 (29.6%) and 47 (32.6%), respectively, had already used this technology. In addition, the IPAQ-Mets and EQ-5D scores were lower in the IIM and PSV groups than in the CTR, and the fatigue severity scale (FSS) scores were higher in the IIM and PSV groups than in the CTR. Patients who used the devices showed FSS scores of 29 (18-40) points, with higher levels of IPAQ-Mets among device users, indicating greater physical activity than among nonusers. Conclusion Based on the results, the use of wearable devices is associated with better fatigue and IPAQ scores. Possibly, the use of such devices can have an impact on better lifestyle habits among these patients.

Diagnostic Approach to Interstitial Lung Diseases Associated with Connective Tissue Diseases.

Interstitial lung disorders are a group of respiratory diseases characterized by interstitial compartment infiltration, varying degrees of infiltration, and fibrosis, with or without small airway involvement. Although some are idiopathic (e.g., idiopathic pulmonary fibrosis, idiopathic interstitial pneumonias, and sarcoidosis), the great majority have an underlying etiology, such as systemic autoimmune rheumatic disease (SARD, also called Connective Tissue Diseases or CTD), inhalational exposure to organic matter, medications, and rarely, genetic disorders. This review focuses on diagnostic approaches in interstitial lung diseases associated with SARDs. To make an accurate diagnosis, a multidisciplinary, personalized approach is required, with input from various specialties, including pulmonary, rheumatology, radiology, and pathology, to reach a consensus. In a minority of patients, a definitive diagnosis cannot be established. Their clinical presentations and prognosis can be variable even within subsets of SARDs.

Imaging Innovations in the Screening, Diagnosis, and Monitoring of Systemic Autoimmune Disease-Related Interstitial Lung Disease

Interstitial lung disease (ILD) is a common and serious complication of systemic autoimmune rheumatic diseases (SARD). The prevalence and prognosis of ILD vary depending on the type and severity of the underlying SARD. Recently, two drugs have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ILD in SARD, and the American College of Rheumatology (ACR) has issued guidelines for the screening and monitoring of these patients. Therefore, it is essential to detect and manage ILD in SARDs as early as possible. High-resolution CT of the chest is the current gold standard test for diagnosis of ILD, yet, it is not uniformly performed as an initial diagnostic test. This review discusses the latest advances in imaging techniques for the diagnosis, assessment, and follow-up of SARD-ILDs.

Incidence and Risk Factors of Mental Illnesses Among Patients with Systemic Autoimmune Rheumatic Diseases: An 18-year population-based study.

This study aimed to assess the incidence and risk factors surrounding mental illnesses in patients diagnosed with systemic autoimmune rheumatic diseases (SARDs). This retrospective cohort study used nationwide, population-based claim data taken from Taiwan's National Health Insurance Research Database (NHIRD) to identify patients certified as having a catastrophic illness for Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), Systemic sclerosis (SSc), Dermatomyositis (DM), Polymyositis (PM) or Sjogren's syndrome (SS) from the years 2002-2020. We furthermore calculated the incidence of mental illness in patients diagnosed with SARDs while exploring factors associated with the development of mental illness using multivariable Cox regression analysis shown as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Among the 28 588 participants, the average age was 47.4 (SD 14.9) years, with most participants being female (76.4%). When compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.20, 95% CI: 1.10-1.32), SS (HR: 1.29, 95% CI: 1.19-1.39), and DM (HR: 1.28, 95% CI: 1.04-1.32) showed a significantly increased risk of developing mental illness. Additionally, when compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.32, 95% CI: 1.21-1.44), SSc (HR: 1.20, 95% CI: 1.02-1.41), SS (HR: 1.17, 95% CI: 1.08-1.26), DM (HR: 1.73, 95% CI: 1.44-2.07), and PM (HR: 1.64, 95% CI: 1.32-2.03) showed a significantly increased risk of antidepressant use. This population-based cohort study revealed that patients diagnosed with SLE, SS and DM had significantly higher risks of developing mental illness when compared with patients with RA.

Antinuclear antibody (ANA) positivity pattern by line immunoassay in a hospital from eastern India: Update from a laboratory perspective.

The existence of more than one antibody in systemic autoimmune rheumatic diseases (SARDs) or connective tissue disease (CTD) along with features of more than one autoimmune disease (AD) in an individual is suggestive of overlap syndrome (OS). Line immunoassay (LIA) can target many autoantibodies in a single approach, thus making the identification of OS feasible. This study aimed to identify the pattern of distribution of antinuclear antibodies by LIA prevalent in a hospital population in eastern India and identify common forms of SARD in this belt based on laboratory findings. A total of 1660 samples received for ANA profile testing by LIA were analysed. Factor analysis was performed with factor loading scores used in the k-means algorithm to identify clustering of various autoantibodies. U1-snRNP positivity was the highest at 16.69%, and the least frequent autoantibody noted was anti-Jo-1 at 0.71% positivity. Based on the outcome of factor analysis, three clusters were determined. Cluster 1 showed a predominance of anti-PM/Scl antibodies, cluster 2 showed a predominance of anti-dsDNA, anti-histone, anti-SmD1, anti-nucleosomes, anti-PCNA, anti-Po, anti-SSA/Ro52, anti-SSA-Ro60, anti-SSB/La, anti-Scl-70, anti-Mi-2, anti-Ku and anti-AMA-M2, and cluster 3 showed a predominance of anti-U1-snRNP. Mixed connective tissue disease (MCTD) and overlap syndrome (OS) are prevalent more than pure form of an AD in our study population. OS may be missed out by monospecific immunoassays and hence adds to diagnostic challenges. LIA may be more useful in identifying specific autoantibodies by a single approach rather than monospecific immunoassays in populations after a positive screen by indirect immunofluorescence (IIF).

The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope.

Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1.

Characteristics of long COVID in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis.

Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients. We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case-control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis. A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs. The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.

Factors Associated With an Electronic Health Record-Based Definition of Postacute Sequelae of COVID-19 in Patients With Systemic Autoimmune Rheumatic Disease.

Many individuals with rheumatic disease are at higher risk for severe acute coronavirus disease 2019 (COVID-19). We aimed to evaluate risk factors for postacute sequelae of COVID-19 (PASC) using an electronic health record (EHR)-based definition. We identified patients with prevalent rheumatic diseases and COVID-19 within the Mass General Brigham healthcare system. PASC was defined by the International Classification of Diseases, 10th revision (ICD-10) codes, relevant labs, vital signs, and medications at least 30 days following the first COVID-19 infection. Patients were followed until the earliest of incident PASC, repeat COVID-19 infection, 1 year of follow-up, death, or February 19, 2023. We used multivariable Cox regression to estimate the association of baseline characteristics with PASC risk. Among 2459 patients (76.37% female, mean age 57.4 years), the most common incident PASC manifestations were cough (14.56%), dyspnea (12.36%), constipation (11.39%), and fatigue (10.70%). Serious manifestations including acute coronary disease (4.43%), thromboembolism (3.09%), hypoxemia (3.09%), stroke (1.75%), and myocarditis (0.12%) were rare. The Delta wave (adjusted hazard ratio [aHR] 0.63, 95% CI 0.49-0.82) and Omicron era (aHR 0.50, 95% CI 0.41-0.62) were associated with lower risk of PASC than the early pandemic period (March 2020-June 2021). Age, obesity, comorbidity burden, race, and hospitalization for acute COVID-19 infection were associated with greater risk of PASC. Glucocorticoid (GC) use (aHR 1.19, 95% CI 1.05-1.34 compared to no use) was associated with greater risk of PASC. Among patients with rheumatic diseases, following their first COVID-19 infection, we found a decreased risk of PASC over calendar time using an EHR-based definition. Aside from GCs, no specific immunomodulatory medications were associated with increased risk, and risk factors were otherwise similar to those seen in the general population.

Fully automated chemiluminescence microarray immunoassay for detection of antinuclear antibodies in systemic autoimmune rheumatic diseases

Abstract Objectives Detection of specific antinuclear antibodies is very important in term of diagnosis, prognosis and management of patients with systemic autoimmune rheumatic diseases. Chemiluminescence microarray immunoassay (CLMIA) is a microdot array-based method that allows simultaneous detection of multiple antinuclear antibodies, which received increasing attention. Methods A CLMIA method that can detect 14 kinds of antinuclear antibodies was established and optimized. Basic performance and diagnostic performance of CLMIA was evaluated by comparing it with line immunoassay (LIA) and indirect immunofluorescence (IIF). Results Through conditional exploration, the optimal blocking time and blocking temperature were determined to be 18 h and 25 °C, respectively. The enzyme-labeled secondary antibody reaction concentration was 0.1 μg/mL, the incubation temperature of serum and enzyme-labeled secondary antibody were 30 °C, and the incubation time of serum and enzyme-labeled secondary antibody were 40 min. After parameter optimization, CLMIA demonstrated high accuracy with a relative bias &lt;15 %; high sensitivity with detection limits below 3 IU/mL for dsDNA and below 1 RU/mL for other ANAs; and high reproducibility with both intra-assay and inter-assay coefficients of variation (CV) &lt;15 %.The CLMIA detection method established in this study was also demonstrated to have good clinical diagnostic performance, showing the highest area under curve (AUC=0.87, p=0.042 and p=0.03). The CLMIA and LIA revealed substantial to good agreements on specific antinuclear antibodies except anti-dsDNA, with the Cohen’s kappa from 0.72 to 0.89. Samples that produced discrepant results between the CLMIA and LIA methods were further analyzed. Upon additional testing, most of these samples were ultimately determined to have been correctly detected by the CLMIA assay rather than the LIA assay, suggesting that CLMIA also shows some superiority in diagnosing dsDNA. Conclusions The CLMIA could become a potential routine method for detecting ANAs with the advantages of good detection performance.