Autoimmune Rheumatic Diseases Research Articles

Determination of antinuclear antibodies: role in modern differential diagnosis of connective tissue autoimmune diseases

There is an increase in autoimmune rheumatic diseases among all age population groups globally. Diagnosis is often difficult, because the early stages of the diseases usually do not have specific symptoms. Often, clinical manifestations of autoimmune diseases and non-autoimmune pathologies have similar symptoms. Therefore, the differential diagnosis could be very difficult. Most often, the determination of antinuclear autoantibodies is used for laboratory diagnosis of connective tissue systemic diseases. Autoantibodies can be detected in patients long time before the appearance of symptoms. The correct diagnosis is very important because the therapy of various nosologies can be different. It is especially significant with the invention of targeted therapy. Further analysis of the diagnostic value of autoantibody determination is very important. This article presents examination and follow-up data of three children. The analysis of medical documentation was carried out. The role of determining autoantibodies in the differential diagnosis of autoimmune connective tissue diseases was analyzed. In the first patient with Sjögren’s syndrome, the clinical picture of the underlying disease developed at least 5 years after the detection of high levels anti-SS-A, SS-B and Ro-52 antibodies (immunoblotting) and the speckled pattern (indirect immunofluorescence assay). In the second patient, antibodies against centromeres (specific markers of systemic scleroderma) appeared at least 2 years before clinical symptoms. In the third patient, the specific markers of systemic scleroderma have been detected for 5 years. There were antibodies against centromeres (immunoblotting), high titer and the centromere pattern (indirect immunofluorescence assay). However, the patient has not developed any clinical symptoms of this disease during all time of observation. Thus, the analysis of the presented clinical cases shows that autoantibodies can be detected in patients long time before the onset of clinical manifestations of a specific autoimmune disease. In all three cases, the first immunological examination has been carried out in the background of the disease symptoms, but they were atypical. Identification of specific autoantibodies, is very important for differential diagnosis. In the absence of clinical symptoms, the presence of autoantibodies, is the reason for dynamic observation of the patients.

The impact of multimorbidity on QoL in inflammatory myopathies: COVAD cluster analysis.

The presence of comorbidities can substantially affect patients' quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs), and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined Basic Multimorbidity (BM) as the presence of ≥ 2 non-rheumatic chronic conditions and Complex Multimorbidity (CM) as the presence of ≥ 3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical Clustering on Principal Components was performed for grouping. Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs, and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (OR: 1.62 vs oAIRDs and 2.95 vs HCs, p< 0.01), BM (OR 1.66 vs oAIRDs and 3.52 vs HCs, p< 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, p< 0.01), and mental health disorders (MHDs) (OR 1.33 vs oAIRDs and 2.63 vs HCs, p< 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all p< 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM, and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

EVUSHELD EFFICACY AND SAFETY IN AUTOIMMUNE RHEUMATIC DISEASES TREATED BY RITUXIMAB: A PROSPECTIVE OBSERVATIONAL TRIAL

Background: B cell depleting therapy (rituximab) results in impaired ability to mount a humoral immune response. Evusheld, tixagevimab 150mg co-packaged with cilgavimab 150mg, is a passive vaccine against SARS-CoV-2. Objective: Evaluate prospectively the efficacy and safety of Evusheld vaccine for preventing or mitigating SARS-COV2 infection in patients with autoimmune rheumatic diseases (AIRD) treated with rituximab. Methods: We compared patients treated with rituximab, who agreed to receive Evusheld, to patients who refused. The primary outcome was the risk of severe COVID19 infection from omicron variant. Results: 45 AIRD patients in the intervention group and 26 in the control group, were recruited. There was no difference between the groups with regard to sex, age, years of rituximab treatment, previous mRNA vaccination and serum immunoglobulins level. No difference in the infection rate was found between intervention group and control group (21 (49%) versus 12 (48%). Four patients had a severe infection, 3 in the control group and 1 in the intervention group. Evusheld reduced the risk for severe infection by 94% (HR 0.06, 95% CI 0.01-0.76, p-value 0.017). No adverse events were reported. Conclusions: Evusheld decreased the risk for severe COVID19 infection in patients with AIRD treated with rituximab in a period in which Omicron BA.5, BQ1 and BQ.1.1 variants were prevalent in Israel, with a favorable safety profile.

Mechanisms underlying sex differences in autoimmunity.

Autoimmune diseases are a leading cause of disability worldwide. Most autoimmune diseases occur more often in women than men, with rheumatic autoimmune diseases being among those most highly expressed in women. Several key factors, identified mainly in animal models and cell culture experiments, are important in increasing autoimmune disease in females. These include sex hormones, immune genes including those found on the X chromosome, sex-specific epigenetic effects on genes by estrogen and the environment, and regulation of genes and messenger RNA by microRNAs found in extracellular vesicles. Evidence is also emerging that viruses as well as drugs or toxins that damage mitochondria may contribute to increased levels of autoantibodies against nuclear and mitochondrial antigens, which are common in many autoimmune diseases. The purpose of this Review is to summarize our current understanding of mechanisms that may determine sex differences in autoimmune disease.

Sjögren disease, new name, new guidelines: Key messages for primary care

Sjögren’s syndrome is increasingly renamed Sjögren disease, as in the recent British Society of Rheumatology guidelines. These guidelines provide evidence-based recommendations for the management of adult and juvenile onset Sjögren disease. Sjögren disease is the second most common autoimmune rheumatic disease (after rheumatoid arthritis), affecting approximately 0.6% of adults, over 90% of whom are women. Sjögren disease can occur as a stand-alone autoimmune disease or overlap with other conditions such as rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis. This article aims to highlight the salient features of the guidelines for primary care physicians to improve the early diagnosis of Sjögren disease and inform the day-to-day management of established cases. The two clinical case scenarios featured in this article should help to highlight the importance of early diagnostic pick up whilst minimising false positive diagnosis and to highlight key messages from the new guidelines. A summary sheet of these guidelines is included in the supplementary material.

Cell-bound complement activation products in antiphospholipid antibody-positive patients without other systemic autoimmune rheumatic diseases.

The objective of this study was to analyze complement activation in antiphospholipid antibody (aPL)-positive patients without other systemic autoimmune rheumatic diseases, using C3/C4 and cell-bound complement activation products (CB-CAPs) (B-lymphocytes [BC4d], erythrocytes [EC4d], and platelets [PC4d]). Persistently aPL-positive patients with or without aPL-related clinical manifestations (thrombotic APS [TAPS], microvascular APS [MAPS], obstetric APS, thrombocytopenia [TP], and/or hemolytic anemia [HA]) were enrolled in a single center study. Blood and clinical data were collected at baseline; a subgroup of patients completed 6- or 12-month follow-up. At baseline, 4/31 (13%) patients had decreased C3/C4, while 7/29 (24%) had elevated BC4d, 11/33 (33%) EC4d, and 12/32 (38%) PC4d. Based on different aPL profiles, all patients with decreased C3/C4 or elevated BC4d, EC4d, and PC4d had triple aPL or isolated lupus anticoagulant positivity. Based on different aPL clinical phenotypes, the number of patients with strongly positive EC4d and PC4d were proportionally higher in those with MAPS/TP/HA, compared to TAPS or no APS. Compared to baseline, the frequencies of BC4d, EC4d, and PC4d positivity were not significantly different in the subgroup of patients during their 6- or 12-month follow-up. There was a weak correlation between C3/C4 and CB-CAPs, especially for PC4d. In summary, complement activation in aPL-positive patients varies based on aPL profiles and clinical phenotypes. Given the higher percentage of aPL-positive patients with abnormal CB-CAPs, compared to C3/C4, and the poor inverse correlation between CB-CAPs and C3/C4, our study generates the hypothesis that CB-CAPs have a role in assessing disease activity and thrombosis risk in aPL-positive patients.

Environment and systemic autoimmune rheumatic diseases: an overview and future directions.

Despite progress in our understanding of disease pathogenesis for systemic autoimmune rheumatic diseases (SARD), these diseases are still associated with high morbidity, disability, and mortality. Much of the strongest evidence to date implicating environmental factors in the development of autoimmunity has been based on well-established, large, longitudinal prospective cohort studies. Herein, we review the current state of knowledge on known environmental factors associated with the development of SARD and potential areas for future research. The risk attributable to any particular environmental factor ranges from 10-200%, but exposures are likely synergistic in altering the immune system in a complex interplay of epigenetics, hormonal factors, and the microbiome leading to systemic inflammation and eventual organ damage. To reduce or forestall the progression of autoimmunity, a better understanding of disease pathogenesis is still needed. Owing to the complexity and multifactorial nature of autoimmune disease, machine learning, a type of artificial intelligence, is increasingly utilized as an approach to analyzing large datasets. Future studies that identify patients who are at high risk of developing autoimmune diseases for prevention trials are needed.

Hydroxychloroquine as an add-on therapy for the induction therapy of MPO-AAV: a retrospective observational cohort study.

The remission rate of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients who received standard induction therapy is far from satisfactory. Improving the remission rate of MPO-AAV patients is essential. Hydroxychloroquine (HCQ), one of the classic antimalarial drugs, has been widely used in various autoimmune rheumatic diseases. This retrospective observational cohort study is aimed to evaluate the efficacy and safety of HCQ during induction treatment for MPO-AAV. The medical records of patients diagnosed with MPO-AAV at Xiangya Hospital, Central South University from January 2021 to September 2023 were collected. They were assigned to the HCQ group or control group according to whether they used HCQ. The patients included were screened by propensity score matching. To evaluate whether MPO-AAV patients benefited from HCQ, we compared the prognosis of the two groups. The adverse effects of HCQ during follow-up were recorded. The composition ratio of complete remission, response and treatment resistance between HCQ group and control group were different statistically (P=.021). There was no significant difference between the two groups in 1-year renal survival (P=.789). The HCQ group had better 1-year patient survival than the control group (P=.049). No serious adverse effects were documented in the HCQ group. HCQ together with standard induction treatment may improve the remission rate of MPO-AAV patients, and HCQ had good safety in our study.

Expert Panel Consensus Statements on Vaccination for Adults with AIRD in India

Introduction: Due to notable distinctions in infection patterns, vaccine accessibility, and approaches to treatment among patients with autoimmune inflammatory rheumatic diseases (AIRD) in India compared to other regions globally, the Indian Rheumatology Association Vaccine (IRAVAC) group was formed to develop expert panel consensus statements on vaccination for adults with AIRDs in India. Methods: The IRAVAC group comprised seven rheumatologists, one epidemiologist, two infectious disease specialists, one clinical virologist, one specialist nurse, and a patient representative. The group determined the scope of the consensus statements, framed the research questions, and assigned a team of few members to review the evidence who designed the search strategy and conducted the systematic literature search and data extraction. Another group of members subsequently reviewed the articles for each vaccine, prepared a summary, generated draft statements, and assigned them an appropriate level of evidence. Eighty-eight such draft statements were circulated to the members of IRAVAC for review and deliberation. The draft statements were revised accordingly, and the final set of 48 statements on vaccinations for eight diseases was voted upon by the IRAVAC group, with a predefined 75% agreement set as a threshold for acceptance. It is envisaged that these consensus statements related to vaccination in AIRD would be helpful not only to rheumatologists in India but also to those in other countries.

Management and associated outcomes of COVID-19 infection among Ghanaian autoimmune rheumatic disease patients.

This study assessed the prevalence of infection, management strategies and associated disease outcomes of COVID-19 among Autoimmune Rheumatic Disease (AIRD) patients in a teaching hospital in Ghana. This was a retrospective cross-sectional study. Rheumatology Unit, Korle Bu Teaching Hospital. Autoimmune Rheumatic Disease patients. Thirty-one (31) out of approximately 1700 AIRD patients in the unit tested positive for COVID-19, registering a COVID-19 prevalence of 1.82%. The majority, 25(80.6%), were females with a mean ± SD age of 41.7 ± 12.8 years. Systemic lupus erythematosus was the most affected autoimmune rheumatic condition, reporting fever as the commonest COVID-19-related symptom. Most participants, 22(71%), were managed by the "self-isolation"/home management" strategy. In comparison, 7(22.5%) were monitored at the hospital, with both strategies having resulted in complete recovery. The remaining 2(6.5%) patients who managed under "intensive care unit" strategy resulted in mortality. These findings highlight the relatively low frequency of COVID-19 infection among AIRD patients, the encouraging recovery, and the low severe disease rates observed within this cohort. Additionally, the outcome of self-isolation and home management strategies underscore the importance of personalised approaches to COVID-19 management in this population. None.

P122 EXPLORING CARDIOVASCULAR RISK ENHANCERS IN WOMEN: EYE-OPENING FINDINGS TO RETHINK ASSESSMENT

Background and Objectives. Traditional cardiovascular risk (CVR) stratification does not consider CVR enhancers (CVRE). Women present under-recognized CVR factors that may lead to developing subclinical vascular lesions such as arterial stiffness (AS). AS is associated with long-term cardiovascular events and can be determined by carotid-femoral pulse wave velocity (cf-PWV). Our objective was to determine cf-PWV in women with low 10-years CVR (10yCVR) with a CVRE and to compare them with a control group. Methods. Multicentric cross-sectional study, carried out in 2023 in Argentina. Group-1: women, 18-59 years-old, office-BP &lt;140/90 mmHg, low (&lt;5%) 10-yCVR using WHO's Calculator for Argentina, with a CVRE: history of gestational hypertension/preeclampsia; previous oncological treatment in current complete remission; autoimmune hematological or rheumatic disease in clinical remission; history of abortions/preterm births; early menopause/menarche; anxiety/depression disorder. Patients with cardiovascular event, chronic renal disease, diabetes, chronic hypertension, target organ lesion, 10-yCVR≥5%, and those on antihypertensive, statins, or aspirin treatment were excluded. Group-2: healthy women who attended routine control. Consecutive sampling. Office-BP were obtained with Omron-M3. cf-PWV was measured non-invasively through Aortic. AS was defined if cf-PWV exceeded 95% confidence interval (95%CI) upper limit for healthy Argentine population. Institutional Research Committee's approval and informed consent were obtained. Data was analyzed using SPSS for Windows. Results. Included 199 women: Group-1 (N=119); Group-2 (N=80). No differences were found between groups concerning age, weight, height, body mass index and heart rate. Group-1 showed higher cf-PWV: 6.89±1.08 vs. 5.56±0.65 (p&lt;0.0001) and higher AS frequency: 57.1% vs. 2.5% (p&lt;0.0001). In multivariate analysis only CVRE maintain related with AS (p&lt;0.0001). A sub-analysis was performed excluding subjects with high-normal office-BP (27.6% of sample): 144 women remained, 77 (53.5%) in Group-1 and 67 (46.5%) in Group-2. Central (aortic) systolic-BP was &lt;121 mmHg in all cases. Group-1 showed higher cf-PWV: 6.62±0.88 vs. 5.59±0.62 (p&lt;0.0001) and AS: 51.9% vs. 1.4% (p&lt;0.0001). Conclusions. Women with CVRE showed greater cf-PWV and higher proportion of AS.

Autoimmune rheumatic transitional care model development

AimTo develop a transitional care model for autoimmune rheumatic disease patients based on the needs analysis.MethodMixed Method, Explanatory sequential design (QUAN-qual) has been conducted. Quantitative data were collected through medical record and structured interviews. Qualitative study has been done through Focused Group Discussion (FGD), based on problems met in previous quantitative study. We have done the coding processed, followed by determining categories and themes to reach the intercoder agreement with peer-debriefing. Analysis of the final results of research was assisted by the external auditor to form a model of care.ResultThe quantitative data collection from 27 patients showed that the transition age was 18–19 year-old, age of onset 4–17 year-old, 23 patients (85, 2%) with SLE, 4 patients (14.8%) with JIA. Two patients (7.4%) had different diagnosis from the pediatric clinic, 1 patient (3.7%) had no diagnosis from previous clinic. Drug switching during transition occurred in 14 patients (51.9%) and 3 patients (11.1%) has no known medication history. Data regarding disease activity at initial diagnosis were not available in 26 patients (96.3%). The combined FGD analysis found several key words related to “the need of change” in RSCM autoimmune rheumatic transitional care.ConclusionA development of transitional care model for autoimmune rheumatic disease consist of documents about service algorithm, transfer documents, systematic work protocols with education check list has been done.

EBNA-1 antibody and autoimmune rheumatic diseases: A Mendelian Randomization Study

BackgroundNumerous studies have investigated a possible correlation between Epstein-Barr virus (EBV) and autoimmune rheumatic diseases (ARDs). However, establishing a cause-and-effect relationship remains a challenging endeavor. This study employs Mendelian randomization to examine the impact of EBV nuclear antigen-1 antibody (EBNA-1) antibody levels on the susceptibility to nine distinct ARDs, including rheumatoid arthritis (RA), primary Sjogren's syndrome (PSS), systemic lupus erythematosus (SLE), undifferentiated reactive arthritis (UA), systemic sclerosis (SSc), adult-onset Still's disease (AOSD), psoriatic arthritis (PsA), dermatomyositis (DM), and ankylosing spondylitis (AS). MethodsThe researchers applied a two-sample Mendelian randomization approach, utilizing online data from separate cohorts of European descent. We drew upon data from GWAS related to EBNA-1 antibody levels and the nine autoimmune-related disorders. Our primary analyses predominantly relied on the Inverse Variance Weighted methodology, complemented by a range of sensitivity assessments. ResultsOur analysis revealed significant direct associations between EBNA-1 antibody levels and the risk of developing PSS (95 % CI: 0.44 to 0.85, p = 0.003), PsA (95 % CI: 0.36 to 0.99, p = 0.044), AS (95 % CI: 0.07 to 0.88, p = 0.031), and UA (95 % CI: 0.56 to 0.96, p = 0.025). These results remained consistent through comprehensive sensitivity analyses. However, no clear associations were found for the other specified conditions. ConclusionsOur findings provide compelling evidence that EBNA-1 antibody levels play a role in developing ARDs. These findings enhance our understanding of ARD pathogenesis and hold substantial promise for developing potential treatment strategies.

Treatment of interstitial lung disease in systemic sclerosis: guidelines and new clinical trial results.

Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). The American College of Rheumatology (ACR), in conjunction with the American College of Chest Physicians (CHEST), recently published clinical practice guidelines for the treatment of adults with systemic autoimmune rheumatic disease-associated ILD, including SSc-ILD. Herein, we summarize evidence from randomized trials evaluating the safety and efficacy of pharmacologic therapies for the treatment of SSc-ILD. In this review, we present findings from recent randomized controlled trials in SSc-ILD. The pharmacologic therapies discussed include immunosuppressive medications (mycophenolate, cyclophosphamide, rituximab, and tocilizumab) and antifibrotic medications (nintedanib and pirfenidone). Randomized trials provide an evidence base for the SSc-ILD treatment recommendations put forth in the ACR/CHEST Guidelines for the treatment of ILD in people with systemic autoimmune rheumatic diseases. These guidelines will help inform clinical practice and highlight areas in which further research is needed.

The Etiology of Intracranial Artery Stenosis in Autoimmune Rheumatic Diseases-An Observational High-Resolution Magnetic Resonance Imaging Study.

Autoimmune rheumatic diseases (AIRD) can cause intracranial artery stenosis (ICAS) and lead to stroke. This study aimed to characterize patients with ICAS associated with AIRD. Utilizing data from a high-resolution magnetic resonance imaging (HRMRI) database, we retrospectively reviewed AIRD patients with ICAS. Stratification into vasculitis, atherosclerosis, and mixed athero-vasculitis subtypes was based on imaging findings, followed by a comparative analysis of clinical characteristics and outcomes across these subgroups. Among 139 patients (45.1±17.3 years; 64.7% females), 56 (40.3%) were identified with vasculitis, 57 (41.0%) with atherosclerosis, and 26 (18.7%) with mixed athero-vasculitis. The average interval from AIRD-onset to HRMRI was 5 years. Patients with vasculitis presented with a younger age of AIRD-onset (34.5±19.4 years), nearly ten years earlier than other groups (P=0.010), with a higher artery occlusion incidence (44.6% vs. 21.1% and 26.9%, P=0.021). Patients with atherosclerosis showed the highest cardiovascular risk factor prevalence (73.7% vs. 48.2% and 61.5%, P=0.021) but lower intracranial artery wall enhancement instances (63.2% vs. 100% in others, P<0.001). The mixed athero-vasculitis group, predominantly male (69.2% vs. 30.4% and 25.6%, P<0.001), exhibited the most arterial involvement (5 arteries per person vs. 3 and 2, P=0.001). Over an average 21-month follow-up, 23 (17.0%) patients experienced stroke events, and 8 (5.9%) died, with the mixed athero-vasculitis group facing the highest risk of stroke events (32.0%) and the highest mortality (12.0%). Intracranial arteries are injured and lead to heterogeneous disease courses when exposed to AIRD and cardiovascular risk factors. While atherosclerosis acceleration is common, vasculitis may further contribute to early-developed occlusion and multiple artery involvement. Varied intracranial arteriopathies may result in different outcomes. ICAS = intracranial artery stenosis; AIRD = Autoimmune rheumatic diseases; HRMRI = high-resolution magnetic resonance imaging.

Clinical Characteristics, Prognostic Factors, and Outcomes of COVID-19 in Autoimmune Rheumatic Disease Patients: A Retrospective Case-Control Study from Astana, Kazakhstan.

Background: Viral infections, including coronavirus disease 2019 (COVID-19), in patients with autoimmune rheumatic diseases (AIRDs) tend to present more severe disease. This study aims to investigate the clinical characteristics and risk factors for severe infection in rheumatologic patients. Methods: We included patients with a diagnosis of AIRD and COVID-19 infection between January 2022 and July 2023. Patients with AIRDs infected with SARS-CoV-2 were matched with control patients of the general population according to age (±5 years) and sex in a 1:1 ratio. Confirmed infection was defined if a patient had a positive polymerase chain reaction (PCR) test. The severity was divided into mild, moderate, severe, and critical according to the guidelines of the United States National Institutes of Health (NIH). Results: A total of 140 individuals (37 males, 103 females; mean age 56.1 ± 11.3 years) with rheumatic disease diagnosed with COVID-19 infection were enrolled in the study. AIRDs included rheumatoid arthritis (RA) (n = 63, 45%), ankylosing spondylitis (AS) (n = 35, 25%), systemic lupus erythematosus (SLE) (n = 26, 8.6%), and systemic sclerosis (SSc) (n = 16, 11.4%). The AIRDs group had more SARS-CoV-2-related dyspnea (38.6%), arthralgia (45.7%), and depression (27.1%) than the control group (p = 0.004). The rate of lung infiltration on radiographic examination was higher in 58 (41.4%, p = 0.005) patients with rheumatic diseases than in those without them. Severe SARS-CoV-2 infection was more common in the AIRDs group than in the control group (22% vs. 12%; p = 0.043). Conclusions: Patients with AIRDs experienced more symptoms of arthralgia, depression, and dyspnea. There was a trend towards an increased severity of the disease in patients with AIRDs. Patients with arterial hypertension, diabetes, chronic lung, and kidney disease, treated with corticosteroids, had a longer duration, and high activity of autoimmune disease had an increased risk of severe COVID-19.

Screening for autoimmune diseases in apparently healthy antinuclear antibody positive individuals.

Anti-nuclear antibodies (ANA) assessed by immunofluorescence (IF) microscopy are associated with systemic autoimmune rheumatic diseases (SARD) and can be detected years before onset of clinical symptoms. Recent data indicate dysregulation of the immune system with increased levels of proinflammatory cytokines, including type I interferons (IFN), in ANA-positive versus ANA-negative individuals. Herein, the aims were to investigate IF-ANA, ANA fine specificities, and IFN-α protein levels in relation to self-reported symptoms, as well as clinical signs, of SARD in a large group of healthy blood donors (HBD). Sera from 825 HBD (48.8% females) were included. IF-ANA was assessed, using HEp-2 cells, according to the routine at the accredited laboratory of Clinical Immunology, Linköping University Hospital. All samples were analyzed for IgG-ANA fine specificities using addressable laser bead assay (ALBIA) at the same laboratory. IFN-α was determined using ELISA. Antibody-positive individuals, and their sex- and age-matched antibody-negative controls, were asked to fill a questionnaire regarding symptoms associated with SARD. In total, 130 HBD (15.8%) were positive with IF-ANA and/or ALBIA. Anti-U1RNP was significantly more common among women. Generally, self-reported symptoms correlated poorly with IF-ANA and/or ALBIA results. Two females with high levels of Ro60/SSA, Ro52/SSA and IFN-α reported mild sicca symptoms and were diagnosed with Sjögren's disease after clinical evaluation. A considerable proportion of apparently HBD are autoantibody positive, but without clear association to self-reported symptoms. Nevertheless, the combination of autoantibodies, relevant symptoms and high IFN-α levels identified the small proportion of individuals with SARD in the study population.

Long-Term Mortality Following SARS-CoV-2 Infection in Rural Versus Urban Dwellers With Autoimmune or Inflammatory Rheumatic Disease: A Retrospective Cohort Analysis From the National COVID Cohort Collaborative.

Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID-19 outcomes. Although rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort. This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID-19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and March 2023. Rural residency was categorized using patient residential zip codes. We adjusted for AIRD medications and glucocorticoid prescription, age, sex, race and ethnicity, tobacco or substance use, comorbid burden, and SARS-CoV-2 variant-dominant periods. Multivariable Cox proportional hazards with inverse probability treatment weighting assessed associations between rurality and two-year all-cause mortality. Among the 86,467 SARS-CoV-2-infected persons with AIRD, we observed a higher risk for two-year post-COVID-19 mortality in rural versus urban dwellers. Rural-residing persons with AIRD had higher two-year all-cause mortality risk (adjusted hazard ratio 1.24, 95% confidence interval 1.19-1.29). Glucocorticoid, immunosuppressive, and rituximab prescriptions were associated with a higher risk for two-year post-COVID-19 mortality, whereas risk with nonbiologic or biologic disease-modifying antirheumatic drugs was lower. Rural residence in people with AIRD was independently associated with higher two-year post-COVID-19 mortality in a large US cohort after adjusting for background risk factors. Policymakers and health care providers should consider these findings when designing interventions to improve outcomes in people with AIRD following SARS-CoV-2 infection, especially among high-risk rural residents.

Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors.

Hepatitis B reactivation (HBVr) constitutes a side effect of the treatment of autoimmune rheumatic diseases. Even though HBVr risk of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) and anti-tumor necrosis factor (anti-TNF) agents has long been established, the risk of targeted synthetic (ts)DMARDs and anti-interleukin (anti-IL) agents remains largely unknown. We conducted a SLR (PubMed, Scopus and EMBASE) and metanalysis to examine the HBVr risk for the following: anti-IL17, anti-IL12/23, anti-IL23 and JAK-inhibitors in patients with chronic HBV infection (HBsAg presence or detectable HBV-DNA) and in patients with prior HBV infection (HBcAb-positive and HBsAg-negative). Meta-analysis was performed using both the fixed and random effects method and was conducted using the R computing language. Overall, our study revealed a low HBVr risk of < 6% in all agents; the risk was significantly higher for people having chronic compared with those with resolved HBV (14,4% vs 5.1%, respectively p< 0.01). There was no difference among different drugs in the HBVr rates [anti-IL-17: 4% (95% CI: 1-9%), anti-IL-12/IL-23: 2% (95% CI: 0-5%), JAK-inhibitors: 4% (95% CI: 1-8%), anti-IL23: 0%]. Of note, HBVr rate reached 28% in patients with chronic HBV who did not receive anti-viral treatment. For patients with resolved hepatitis the respective percentage was 4.7%. Overall, our meta-analysis shows that patients with chronic HBV receiving anti-IL-17, anti-IL-12/23, anti-IL-23 and JAK-inhibitors have significant risk for HBVr, especially if they are not under anti-viral treatment. In contrast, resolved HBV seems to offer minor risk for HBVr even without anti-viral treatment.

Clinical outcomes and risk factors in patients with COVID-19 and autoimmune rheumatic diseases: insights from a major Australian hospital study.

Patients with autoimmune inflammatory rheumatic disease (AIIRD) are at higher risk of severe infections because of their underlying diseases and immunosuppression. Our objective was to elucidate the epidemiological and clinical characteristics of patients with AIIRD presenting with COVID-19 and their relation to disease severity. We explored whether variables, including underlying diagnosis, disease-modifying antirheumatic drugs (DMARDs) and COVID-19 vaccine status, were associated with more severe forms of COVID-19 infection. Between 1 January 2020 and 30 June 2022, 151 patients with AIIRD and COVID-19 infection were analysed using a binary regression model and a multinomial regression model. The average age was 61.5 years, and average Charlson Comorbidity Index (CCI) was 2.1; 106 (70.2%) patients were diagnosed with rheumatoid arthritis (RA), and 70 (46.4%) patients were receiving prednisolone. In the multivariable logistic regression model, ages between 50 and 69 years (odds ratio (OR) = 5.85; 95% confidence interval (CI) = 1.35-25.25) and older than 70 years (OR = 5.29; 95% CI = 1.21-23.14), prior prednisolone treatment (OR = 7.09; 95% CI = 2.63-19.11) and vaccination status including one and two doses (OR = 0.19; 95% CI = 0.05-0.69) and three and four doses (OR = 0.09; 95% CI = 0.02-0.35) were all statistically significant factors related to changes in the severity level of COVID-19. Severity of COVID-19 infection in patients with AIIRD is affected by age, background steroid use and vaccination status. Factors including sex, comorbidity, diagnosis of AIIRDs and use of DMARDs, including conventional synthetic, biologics and targeted DMARDs, were not significantly associated with COVID-19 severity.