Systemic Autoimmune Rheumatic Diseases Research Articles

Зміни ендотелію судин нирок і показники ендотеліальної васкулярної дисфункції при системних автоімунних ревматичних хворобах

Метою роботи стала оцінка характеру морфологічних змін ендотелію капілярів й артеріол нирок при системному червоному вовчаку, ревматоїдному артриті, геморагічному васкуліті та мікроскопічному поліангіїті, зв’язок з клініко-лабораторними чинниками перебігу захворювань і вплив системної ендотеліальної дисфункції судин. Остання в цих групах хворих відповідно має місце в 39, 35, 52 та 100 % випадків, беручи участь в патогенетичних побудовах нефропатії, щільно пов’язана з системними клініко-інструментальними проявами ангіопатії, а проліферацію ендотелію капілярів й артеріол нирок, відкладання в ньому імуноглобулінів і компонентів комплементу залежно від нозологічних форм системних автоімунних ревматичних захворювань визначають рівні в крові судинного ендотеліального фактора зростання, ендотеліну-1, гомоцистеїну, Е- і Р-селектинів.

Anti-DFS70 Antibodies for Differentiating Systemic Autoimmune Rheumatic Disease in Patients with Positive ANA Tests: A Systematic Review and Meta-Analysis.

Anti-DFS70 antibodies have been proposed as a marker to exclude systemic autoimmune rheumatic disease (SARD). We conducted this systematic diagnostic test accuracy review and meta-analysis to determine the performance of anti-DFS70 antibodies in patients with a positive anti-nuclear antibody (ANA) test result to exclude SARD. We searched PubMed, Embase, Web of Science, Scopus and the Cochrane Library up to 22 February 2021, and included studies examining the diagnostic accuracy of anti-DFS70 antibodies in patients with a positive ANA test result. The results were pooled using a hierarchical bivariate model and plotted in summary receiver operating characteristic curves. R software and Stata Statistical Software were used for the statistical analysis. Eight studies with 4168 patients were included. The summary sensitivity was 0.19 (95% confidence interval: 0.12–0.28) and the specificity was 0.93 (95% confidence interval: 0.88–0.96). The area under the curve was 0.69 (95% confidence interval: 0.64–0.72). The meta-regression analysis showed that targeting only ANA-associated rheumatic disease was associated with higher specificity. In addition, the studies with a non-SARD prevalence of <80% and using a chemiluminescence assay were associated with higher specificity. Anti-DFS70 antibodies have high specificity for the exclusion of SARD among patients presenting with a positive ANA test, but the sensitivity is low.

Occurrence and Antigenic Specificity of Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) in Systemic Autoimmune Diseases.

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides (n = 24), systemic lupus erythematosus (n = 28), antiphospholipid syndrome (n = 5), Sjögren’s syndrome (n = 7), rheumatoid arthritis (n = 3), systemic scleroderma (n = 1), sarcoidosis (n = 1) and Hashimoto′s thyroiditis (n = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens.

Novel role of long non-coding RNAs in autoimmune cutaneous disease.

Systemic autoimmune rheumatic diseases (SARDs) are a heterogeneous group of chronic multisystem inflammatory disorders that are thought to have a complex pathophysiology, which is not yet fully understood. Recently, the role of non-coding RNAs, including long non-coding RNA (lncRNA), has been of particular interest in the pathogenesis of SARDs. We aimed to summarize the potential roles of lncRNA in SARDs affecting the skin including, systemic sclerosis (SSc), dermatomyositis (DM) and cutaneous lupus erythematosus (CLE). We conducted a narrative review summarizing original articles published until July 19, 2021, regarding lncRNA associated with SSc, DM, and CLE. Several lncRNAs were hypothesized to play an important role in disease pathogenesis of SSc, DM and CLE. In SSc, Negative Regulator of IFN Response (NRIR)was thought to modulate Interferon (IFN) response in monocytes, anti-sense gene to X-inactivation specific transcript(TSIX) to regulate increased collagen stability, HOX transcript antisense RNA(HOTAIR) to increase numbers of myofibroblasts, OTUD6B-Anti-Sense RNA 1 to decrease fibroblast apoptosis, ncRNA00201 to regulate pathways in SSc pathogenesis and carcinogenesis, H19X potentiating TGF-β-driven extracellular matrix production, and finally PSMB8-AS1 potentiates IFN response. In DM, linc-DGCR6-1 expression was hypothesized to target the USP18 protein, a type 1 IFN-inducible protein that is considered a key regulator of IFN signaling. Additionally, AL136018.1 is suggested to regulate the expression Cathepsin G, which increases the permeability of vascular endothelial cells and the chemotaxis of inflammatory cells in peripheral blood and muscle tissue in DM. Lastly, lnc-MIPOL1-6 and lnc-DDX47-3 in discoid CLE were thought to be associated with the expression of chemokines, which are significant in Th1 mediated disease. In this review, we summarize the key lncRNAs that may drive pathogenesis of these connective tissue diseases and could potentially serve as therapeutic targets in the future.

Role of anti-nuclear antibody-dense fine speckled pattern for diagnosing systemic autoimmune rheumatic disease

Role of anti-nuclear antibody-dense fine speckled pattern for diagnosing systemic autoimmune rheumatic disease

Clinical significance of anti-NOR90 antibodies in systemic sclerosis and idiopathic interstitial pneumonia.

Anti-NOR90 antibodies are usually found in patients with SSc; however, their clinical relevance remains obscure. We developed an ELISA for measuring them to investigate the clinical features of patients with anti-NOR90 antibodies. Serum samples from 1252 patients with various conditions from Nagoya University Hospital and 244 patients with idiopathic interstitial pneumonia (IIP) from Tosei General Hospital were included. Anti-NOR90 antibodies were assayed by an ELISA using the recombinant protein produced by in vitro transcription/translation. Five (0.4%) patients in the Nagoya University Hospital cohort had anti-NOR90 antibodies. One patient with diffuse cutaneous SSc, three with limited cutaneous SSc, and one with Raynaud's disease were positive for anti-NOR90 antibodies. Anti-NOR90 antibodies were found more frequently in patients with systemic scleroderma-spectrum disorders (SSDs) than without SSDs (5/316 vs 0/936, P <0.00101) and were found more frequently in patients with SSc than without SSc (4/249 vs 0/528, P <0.0104) in the systemic autoimmune rheumatic diseases cohort. Three of the four anti-NOR90-positive SSc patients had interstitial lung disease (ILD), and two of those four had cancer. Three (1.2%) patients in the Tosei General Hospital cohort had anti-NOR90 antibodies. All three of the anti-NOR90-positive IIP patients had gastrointestinal tract involvement, and two of those three had cancer or skin lesions observed in SSc. Although anti-NOR90 antibodies are rarely found in clinics, our ELISA is useful for their detection. Further studies are needed to confirm the association of anti-NOR90 antibodies with ILD and cancer in SSc and IIP patients.

Prevalence and clinical impact of systemic autoimmune rheumatic disease in patients with silicosis

BackgroundSilicosis is associated with an increased risk of developing systemic autoimmune rheumatic disease (SARD). The prognostic implications of this association are poorly characterized. The aim of this study was to determine the prevalence of SARD and autoimmune markers in a cohort of patients with exposure to silica and assess their impact on prognosis. MethodWe performed a prospective observational study of all patients attending the dedicated silicosis clinic of our pulmonology unit between 2009 and December 2017. Diagnosis was confirmed by a rheumatologist according to Spanish Rheumatology Society criteria. Autoimmune markers, pulmonary function tests, radiological progression, visits to the emergency department and primary care center, and hospital admissions for respiratory causes, and mortality were analyzed. ResultsOverall, 489 cases of silicosis and 95 cases of exposure were studied. In total, 54 (11.0%) patients with silicosis had SARD: 12 (2.4%) rheumatoid arthritis, 10 (2.0%) systemic lupus erythematosus, 10 (2.0%) systemic sclerosis, 3 (0.6%) Sjögren syndrome, 2 (0.4%) vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA +), 6 (1.2%) psoriatic arthritis, 3 (0.6%) ankylosing spondylitis, and 8 (1.6%) other autoimmune diseases with no special features. The patients with SARD visited the emergency room more often (63.0% vs. 42.5%; p = 0.004), and progressed more rapidly (22.2 vs. 11.7%; p = 0.030). ConclusionsThe presence of systemic rheumatic autoimmune diseases involves radiological progression and a higher clinical impact.

Investigation of the Clinical Significance of Anti-Dense Fine Speckled 70 (anti-DFS70) Autoantibody and Determination of Accompanying Pathologies

Autoantibodies targeting nuclear and cytoplasmic autoantigens are used as markers in the diagnosis and classification of systemic autoimmune rheumatic diseases (SARD). The dense fine speckled (DFS) pattern is characterized by the fine-granular fluorescence of the nuclei in the interphase and the metaphase chromatin. DFS70 antibodies have been reported in healthy individuals, various autoimmune disorders, infection, cancer and inflammatory conditions. But there is still lack of information about its clinical significance. This study aimed to investigate the clinical significance of anti-DFS70 autoantibodies and the determination of accompanying pathologies. A total of 5710 serum samples routinely requested for ANA screening were tested between 2017 and 2019. Antinuclear antibody (ANA) and dsDNA were performed by indirect immunofluorescence method (IIF) (Euroimmun, Germany). Immunoblot (IB) method was used for the extractable nuclear antigen profile (ENA) (Euroimmun, Germany). Demographic and clinical data, were investigated from the medical records. Among 5710 samples tested for ANA, 23.7% were ANA positive by IIF. Mean age of the patients were 47.9 and 79.5% were female. Only 8.1% of the study group had SARD. The frequency of DFS pattern by ANA-IIF was 6.0% (342/5710), (mean age ± SD= 44.4 ± 16.7, 88% female). DFS70 pattern-positive patients were sub-grouped according to their diagnosis. SARD were detected 10.8% (mean age ± SD= 55.12 ± 14.10) in DFS70 pattern positive patient group (RA 6.1%, SS 2.6%, SLE 0.9%, SSc 0.6%, UCTD 0.6%). Autoantibodies accompanying anti-DFS70 antibody were determined as Ro-52, SS-A, nucleosome, histone, AMA-M2, dsDNA, respectively. Non-SARD diseases were determined in 89.2% of the patients with positive DFS70 pattern. Non-SARD diseases were detected as musculoskeletal complaints (47.4%), other rheumatic diseases like fibromyalgia (14.3%), dermatological diseases (9.4%), gastrointestinal system diseases (5.6%), hematological disorders (3.8%), thyroid /parathyroid diseases (3.5%), allergic diseases (2.3%), neurological diseases (2.3%) and neoplasia (breast cancer) (0.6%). The anti-DFS70 autoantibody is widely used to exclude the diagnosis of SARD in the absence of concomitant SARD-related autoantibodies. It has been observed that anti-DFS70 autoantibody may be associated with non-SARD rheumatic diseases and in many diseases (dermatological, gastrointestinal system, hematological, thyroid diseases) related to other systems. Therefore it is essential to evaluate these pathologies in patients positive for anti-DFS70 antibodies.

COVID-19 vaccine hesitancy in patients with systemic autoimmune rheumatic disease: an interview-based survey.

Patients with a systemic autoimmune rheumatic disease (AIRD) are vulnerable to SARS Cov-2 infection. Vaccination against this infection can prevent the patients from developing severe disease. But vaccine hesitancy in this group can emerge as a hurdle. So there is a need to understand the perception regarding vaccination in AIRD patients. The study is an interview-based survey done in AIRD patients and a control group from the general population. The questionnaire included the subject’s demographic details, duration, diagnosis, the activity of AIRD, and questions regarding the perception of the vaccination. The survey included 280 patients with AIRD and 102 control subjects. 54% (152/280) of the patients and 67% (68/102) of the controls were willing to get vaccinated (p = 0.03). Patients > 45-years of age were more willing to vaccinate than those with age ≤ 45-years (61.9% vs. 44.8%; p = 0.001). Patients with lower education had more vaccine hesitancy than those with graduation and above (38% vs. 69%; p < 0.001). The common reason for vaccine hesitancy was not-yet-decided, fear related to vaccine side-effects, and disease worsening. 29% (82/280) patients were already vaccinated, out of which 35% (35/82) had mild events (fever/myalgia/headache). AIRD patients had fewer side effects than controls, and disease flare was seen in only one patient. Thus, educating AIRD patients regarding the pros and cons of vaccination, particularly concerning immunological disease, can help us overcome vaccine hesitancy. The message should clearly penetrate that there is a negligible risk of AIRD-flares with the COVID-19 immunization and the side effects are mild and manageable.

Serological abnormalities that predict progression to systemic autoimmune rheumatic diseases in antinuclear antibody-positive individuals.

We investigated the autoantibody (autoAb) profiles in ANA+ individuals lacking systemic autoimmune rheumatic disease (SARD) and early SARD patients to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next 2 years in ANA+ individuals. Using custom antigen (Ag) microarrays, 144 IgM and IgG autoAbs were surveyed in 84 asymptomatic and 123 symptomatic (48 UCTD and 75 SARD patients) ANA+ individuals. AutoAbs were compared in ANA+ individuals lacking a SARD diagnosis with ≥2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset. We show that ANA+ individuals have autoAb to many self-Ags that are not being captured by current screening techniques and very high levels of these autoAbs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more autoAgs than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of autoAbs. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years of follow-up the levels of autoAbs remained remarkably stable regardless of whether individuals progressed or not. Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing.

Desenlaces hospitalarios en pacientes evaluados por reumatología en una cohorte histórica colombiana

IntroductionHospitalized patients with systemic autoimmune rheumatic diseases (SARDs) generate high impact in clinical terms. ObjectivesTo characterize the study population and estimate risk factors associated with the presence of adverse outcomes in hospitalized patients consulting rheumatology at Clínica Imbanaco between January 2013 and December 2019. MethodsWe analysed a historical cohort of hospitalized patients who were evaluated by rheumatology. The population was classified as follows: group 1, patients with new onset diagnosed SARDs; group 2, patients with known diagnosed SARDs; group 3, patients without diagnosed SARDs; and group 4, patients with unconfirmed suspicion of SARDs. A composite adverse outcome was defined if at least one of the following occurred: 1) hospital mortality, 2) admission to the intensive care unit, 3) hospital infection, or 4) readmission. ResultsInformation was collected from 327 hospitalization events (307 patients). The median age was 48 (34-63) years and 222 (72.3%) were women. The composite adverse outcome occurred in 136 (41.5%) hospitalization events. Group 2 had the highest number of adverse outcomes (61/128; 47.6%). The variables associated with the worst outcomes were cardiovascular diagnosis at admission (OR=4.63; CI: 1.60-13.43; p=.005), longer hospital stay (OR=1.04; CI: 1.01-1.07; p=.005), and atreating specialty other than internal medicine (OR=2.79; CI: 1.26-6.17; p=.011). Male sex (OR=.29; CI: .12-.66; p=.004), having special health coverage (OR=.39; CI: .15-.99; p=.047), and haemoglobin>11.4g/dL (OR=.82; CI: .69-.99; p=.039) were the factors associated with lower odds of developing the composite outcome. ConclusionsIn this historical cohort, the group of patients with known diagnosed SARDs presented a higher number in percentage terms of adverse outcomes. The most frequent adverse outcomes were admission to the ICU and hospital readmission.

Assessment of antinuclear antibodies (ANA): National recommendations on behalf of the Croatian society of medical biochemistry and laboratory medicine.

Antinuclear antibodies (ANA) represent a family of autoantibodies targeting ubiquitous cellular constituents and are a hallmark of systemic inflammatory autoimmune rheumatic diseases named connective tissue diseases (CTD). The gold standard method for ANA determination is indirect immunofluorescence (IIF) on the human laryngeal epidermoid carcinoma cell line type 2 substrate (HEp-2), but with increasing demand for ANA testing, novel methods eased for automation emerged, which allows testing by staff less experienced in this specific field of laboratory diagnostic. In 2016 The working group (WG) for laboratory diagnostics of autoimmune diseases as part of the Committee for the Scientific Professional Development of the Croatian Society of Medical Biochemistry and Laboratory Medicine (CSMBLM) published the data of a survey regarding general practice in laboratory diagnostics of autoimmune diseases in Croatia. Results indicated high diversity in the performance of autoantibody testing as well as reporting of the results and indicated the need of creating recommendations for the assessment of ANA that would help harmonize diagnostics of systemic autoimmune rheumatic diseases in Croatia. This document encompasses twenty-seven recommendations for ANA testing created concerning indications for ANA testing, preanalytical, analytical, and postanalytical issues, including rational algorithm and quality control assurance. These recommendations are based on the relevant international recommendations and guidelines for the assessment of ANA testing and relevant literature search and should help to harmonize the approach in ANA testing and clarify differences in interpretation of the results obtained using different methods of determination.

POS0050 ARE PATIENTS WITH IMMUNE MEDIATED INFLAMMATORY DISEASES (IMID) MORE LIKELY TO RECEIVE COVID-19 TESTS AND TEST POSITIVE FOR SARS-COV-2? A MATCHED POPULATION-BASED STUDY

Background:Population-based data about the COVID-19 risk in patients with IMID remain scarce.Objectives:To investigate the cumulative incidence and risk factors for laboratory-confirmed COVID-19 infection and SARS-CoV2 testing in patients with IMID compared with matched non-IMID patients from the general population.Methods:A population-based, matched cohort study was conducted using health administrative data from adults living in Ontario, Canada from January to December 2020. Cohorts for each of the following IMID were assembled: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases (including lupus, systemic sclerosis, Sjogren’s, inflammatory myositis), multiple sclerosis (MS), iritis, inflammatory bowel disease (IBD), polymyalgia rheumatica (PMR) and vasculitis. Each patient was matched with 5 non-IMID comparators based on age, sex, area of residence and living in long term care (LTC). Standardized cumulative rates of testing for SARS-CoV2, and for receiving a positive test between IMID and non-IMID were compared between IMID and non-IMID patients. Multivariable logistic regression analyses assessed sociodemographic factors associated with COVID-19 testing and positivity.Results:A total of 493,499 IMID patients and 2,466,946 non-IMID comparators were assessed. Significantly more IMID patients versus non-IMID were tested for SARS-CoV2 (27.4% vs. 22.7%), while the proportions of those positive for COVID-19 were identical (0.9% of all patients in both groups). Overall, IMID patients were more likely to undergo SARS-CoV2 testing (odds ratio (OR) 1.28, 95% CI 1.27, 1.29), but their overall risk of laboratory-confirmed COVID-19 was not elevated (OR 0.97 (95% CI 0.93, 1)). However, the risk of laboratory-confirmed COVID-19 infection was lower in IBD (OR 0.75), MS (OR 0.77) and psoriasis (OR 0.94) and marginally higher in RA (OR 1.07) and iritis (OR 1.13) compared with non-IMID comparators (Figure 1A). The highest standardized rates of COVID-19 infection were found in vasculitis (115 per 10,000 patients) and iritis (109 per 10,000 patients) (Figure 1B). Risk factors for COVID-19 infection included younger age, living in LTC, multimorbidity, urban living and lower income (Table 1).Conclusion:Patients across all IMID were more likely to be tested for COVID-19 versus non-IMID patients. IMID patients were not at higher risk for testing positive for COVID-19 as an overall group, yet risk varied across disease subgroups.Table 1.Factors associated with COVID-19 infection in IMID vs. Non-IMID – Multivariable Logistic RegressionVariableORCI 95%IMID vs. Non-IMID0.970.93, 1.00Age (10-year increase)0.890.89, 0.90Sex: Female vs. Males0.950.93, 0.97LTC18.6417.9, 19.42ADG score:•5-9 vs. 0-41.401.35, 1.45•10-14 vs. 0-41.731.67, 1.80•15+ vs. 0-41.181.13, 1.23Urban vs. Rural3.493.26, 3.72Income quintile•Quintile 2 vs. 10.920.89, 0.96•Quintile 3 vs. 10.900.86, 0.93•Quintile 4 vs. 10.730.70, 0.76•Quintile 5 vs. 10.600.58, 0.63ADG - Aggregated Diagnosis Groups; IMIDs – Immune medicated inflammatory disease; LTC – long term careAcknowledgements:The study is supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Parts of this material are based on data and information compiled and provided by MOHLTC and the Canadian Institute for Health Information. The opinions, results and conclusions reported in this paper are those of the authors and are independent of the funding or data sources; no endorsement is intended or should be inferred.Disclosure of Interests:None declared.

OP0285 COVID-19 HOSPITALIZATIONS, ICU ADMISSION, AND DEATH AMONG PATIENTS WITH IMMUNE MEDIATED INFLAMMATORY DISEASES (IMID) – A POPULATION-BASED STUDY

Background:It remains unclear whether patients with IMID are at greater risk for severe COVID-19.Objectives:To investigate the risk of COVID-19 hospitalizations and their outcomes in patients with IMID compared with matched non-IMID patents from the general population.Methods:A population-based, matched cohort study was conducted in adults living in Ontario, Canada using health administrative data. Ten cohorts of the following IMID were assembled: rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases (SARDs, including systemic lupus, systemic sclerosis, Sjogren’s, myositis), multiple sclerosis (MS), iritis, inflammatory bowel disease, polymyalgia rheumatica (PMR), and vasculitis (including giant cell arteritis and other types of vasculitidies). Each patient was matched with 5 non-IMID comparators based on age, sex, area of residence and living in long-term care (LTC). Patients who were admitted to hospital from January 1st to July 31th, 2020 and had ICD-10 COVID-19 diagnosis codes (U07.2 or U07.1) were identified. Among those with COVID-19 hospitalizations, we determined those with admissions to intensive care unit or required mechanical ventilation or died in hospital (‘complicated hospitalization’). Age-sex-standardized rates were compared between IMID and non-IMID patients and risk factors for hospitalizations were identified by multivariable logistic regression analysis.Results:In total, 493,499 IMID (417 hospitalized) and 2,466,946 non-IMID patients (1,519 hospitalized) were assessed. The age-sex-standardized rate of COVID-19 hospitalization was higher in IMID (6.4 per 10,000, 95% confidence interval (CI) 5.8, 7.2) versus non-IMID patients (4.8 per 100,000, 95% CI 4.5, 5). The highest rates of hospitalizations were found in vasculitis (18/10,000), MS (16.7/10,000) and PMR (10.1/10,000). IMID diagnosis was associated with 37% higher risk of being hospitalized for COVID-19 (Odds Ratio (OR) 1.37, 95% CI 1.23, 1.53) (Figure 1). This risk was slightly attenuated after adjusting for sociodemographic factors and comorbidities but remained elevated by 23% compared to non-IMID (OR 1.23, 95% CI 1.10, 1.37). The risk for hospitalizations was increased in RA, vasculitis, SARDs, PsA, MS and iritis (Figure 1). Risk factors for COVID-19 hospitalizations included older age, male sex, lower income, multimorbidity and living in long-term care (Table 1). The risk for complicated COVID-19 hospitalizations was higher by 21% in IMID patients (OR 1.21, 95% CI 1.02, 1.43), however, this association was attenuated after adjustment for demographics and comorbidities (OR 1.08).Table 1.Risk Factors for COVID-19 Hospitalizations in IMIDs vs. non-IMIDsVariableOR95% CIIMIDs vs. Non-IMID1.231.10, 1.37Age (10 yrs)1.491.44, 1.54Sex: Female0.680.62, 0.75Long term care resident8.287.32, 9.37ADG: 5-9 vs. 0-41.451.22, 1.7110-14 vs. 0-42.261.92, 2.6715+ vs. 0-43.232.73, 3.82Income (quintile) Quintile 2 vs. 10.820.73, 0.93 Quintile 3 vs. 10.760.67, 0.86 Quintile 4 vs. 10.560.48, 0.64 Quintile 5 vs. 10.460.40, 0.54Urban vs. rural4.333.32, 5.67ADG - Aggregated Diagnosis GroupsConclusion:Patients with IMID were at higher risk of being hospitalized with COVID-19 and for having complicated hospitalizations. Hospitalization risk was partially independent of their comorbid conditions.Acknowledgements:The study is supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Parts of this material are based on data and information compiled and provided by MOHLTC and the Canadian Institute for Health Information. The opinions, results and conclusions reported in this paper are those of the authors and are independent of the funding or data sources; no endorsement is intended or should be inferred.Disclosure of Interests:None declared

Presence of anti-TIF-1γ, anti-Ro52, anti-SSA/Ro60 and anti-Su/Ago2 antibodies in breast cancer: a cross-sectional study

Objectives The presence of myositis-specific antibodies (MSA), was recently reported in healthy individuals, cancer patients without myopathy and paraneoplastic rheumatic syndromes. We sought to analyze the frequency of MSA, myositis-associated antibodies (MAA) and autoantibodies related to systemic autoimmune rheumatic diseases (SARD) in breast cancer patients. Methods One hundred fifty-two breast cancer patients were enrolled in a cross-sectional study. Clinical information was collected, and autoantibodies tested by immunoprecipitation of an 35S-methionine-labeled K562 cell extract, enzyme-linked immunosorbent assay (ELISA) and Western blot when indicated. All statistical tests were performed using the software statistical package for the social science (SPSS) ver. 19.0 (IBM Inc., NYSE, USA). Results Autoantibodies associated with SARD: anti-52 kD ribonucleoprotein/tripartite motif-containing 21 (anti-Ro52/TRIM21) was found in 5.9% (9/152), anti-Sjögren syndrome-related antigen A/60 kD ribonucleoprotein antibody (anti-SSA/Ro60) in 3.9% (6/152) and anti-Su antigen/Argonaute 2 antibody (anti-Su/Ago2) in 2.6% (4/152). Meanwhile, anti-transcription intermediary factor-1γ (anti-TIF-1γ, p155/140) antibody was positive in 2 cases and anti-polymyositis/scleroderma antibody was detected in one case. As a whole, 14.47% (22/152) of breast cancer patients showed autoantibodies associated with SARD. These specific autoantibodies were not associated with the presence of rheumatic diseases except one rheumatoid arthritis patient positive for anti-Ro52/TRIM21. Conclusions Autoantibodies to TIF-1γ were found in two patients with breast cancer without dermatomyositis (DM). More common specificities were autoantibodies anti-SSA/Ro60, anti-Ro52/TRIM21 and anti-Su/Ago2. More studies are needed in order to establish the biological meaning of the presence of SARD-associated autoantibodies in breast cancer.

Adiponectin Deregulation in Systemic Autoimmune Rheumatic Diseases.

Deregulation of adiponectin is found in systemic autoimmune rheumatic diseases (SARDs). Its expression is downregulated by various inflammatory mediators, but paradoxically, elevated serum levels are present in SARDs with high inflammatory components, such as rheumatoid arthritis and systemic lupus erythematosus. Circulating adiponectin is positively associated with radiographic progression in rheumatoid arthritis as well as with cardiovascular risks and lupus nephritis in systemic lupus erythematosus. However, in SARDs with less prominent inflammation, such as systemic sclerosis, adiponectin levels are low and correlate negatively with disease activity. Regulators of adiponectin gene expression (PPAR-γ, Id3, ATF3, and SIRT1) and inflammatory cytokines (interleukin 6 and tumor necrosis factor α) are differentially expressed in SARDs and could therefore influence total adiponectin levels. In addition, anti-inflammatory therapy could also have an impact, as tocilizumab treatment is associated with increased serum adiponectin. However, anti-tumor necrosis factor α treatment does not seem to affect its levels. Our review provides an overview of studies on adiponectin levels in the bloodstream and other biological samples from SARD patients and presents some possible explanations why adiponectin is deregulated in the context of therapy and gene regulation.

Immune Axonal Neuropathies Associated With Systemic Autoimmune Rheumatic Diseases.

Immune axonal neuropathies are a particular group of immune-mediated neuropathies that occasionally accompany systemic autoimmune rheumatic diseases such as connective tissue dissorders and primary systemic vasculitides. Apart from vasculitis of vasa nervorum, various other mechanisms are involved in their pathogenesis, with possible therapeutic implications. Immune axonal neuropathies have highly heterogeneous clinical presentation and course, ranging from mild chronic distal sensorimotor polyneuropathy to severe subacute mononeuritis multiplex with rapid progression and constitutional symptoms such as fever, malaise, weight loss and night sweats, underpinning a vasculitic process. Sensory neuronopathy (ganglionopathy), small fiber neuropathy (sensory and/or autonomic), axonal variants of Guillain-Barré syndrome and cranial neuropathies have also been reported. In contrast to demyelinating neuropathies, immune axonal neuropathies show absent or reduced nerve amplitudes with normal latencies and conduction velocities on nerve conduction studies. Diagnosis and initiation of treatment are often delayed, leading to accumulating disability. Considering the lack of validated diagnostic criteria and evidence-based treatment protocols for immune axonal neuropathies, this review offers a comprehensive perspective on etiopathogenesis, clinical and paraclinical findings as well as therapy guidance for assisting the clinician in approaching these patients. High quality clinical research is required in order to provide indications and follow up rules for treatment in immune axonal neuropathies related to systemic autoimmune rheumatic diseases.

The negative impact of Sjögren’s syndrome on female sexuality

*Doina RAMBA NIȚESCU1 MD,Ph.D., Dr. Veronica PAT2MD 1. Department of Internal Medicine “Colentina” Clinical Hospital-Internal Medicine Clinic 2. Clinic of Dentistry, Tel Aviv Abstract Women suffering from systemic autoimmune rheumatic diseases, including primary Sjögren’s syndrome (pSS), have significant deterioration of their sexual activity that leads to impaired quality of life. In rheumatology, sexual disability is Read More

Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?

The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is poor in those receiving immunosuppressive therapy and glucocorticoids in particular. Despite the effectiveness of cotrimoxazole against PJP, the risk of adverse effects remains significant, and no consensus has emerged regarding the need for PJP prophylaxis in SARD patients undergoing immunosuppressor therapies.Objective:To evaluate the efficacy and safety of cotrimoxazole prophylaxis against PJP in SARD adult patients receiving immunosuppressive therapies. Methods: We performed a systematic review, consulting MEDLINE, EMBASE, and Cochrane Library databases up to April 2020. Outcomes covered prevention of PJP, other infections, morbidity, mortality, and safety. The information obtained was summarized with a narrative review and results were tabulated. Of the 318 identified references, 8 were included. Two were randomized controlled trials and six observational studies. The quality of studies was moderate or low. Despite disparities in the cotrimoxazole prophylaxis regimens described, results were consistent in terms of efficacy, particularly with glucocorticoid doses > 20mg/day. However, cotrimoxazole 400mg/80mg/day, prescribed three times/ week, or 200mg/40mg/day or in dose escalation, exhibited similar positive performances. Conversely, cotrimoxazole 400mg/80mg/day showed higher incidences of withdrawals and adverse effects. Cotrimoxazole prophylaxis against PJP exhibited efficacy in SARD, mainly in patients taking glucocorticoids ≥ 20mg/day. All cotrimoxazole regimens exposed seemed equally efficacious, although, higher quality trials are needed. Adverse effects were observed 2 months after initiation, particularly with the 400mg/80mg/day regimen. Conversely, escalation dosing or 200mg/40mg/day regimens appeared better tolerated.

Biologics During Pregnancy and Breastfeeding Among Women With Rheumatic Diseases: Safety Clinical Evidence on the Road.

Females are generally more affected by autoimmune diseases, a fact that underlines the relationship with pregnancy and the safety of anti-rheumatic drugs in pregnancy and lactation. Biologic therapies are increasingly prescribed to treat and maintain remission in a significant number of systemic autoimmune rheumatic diseases. The experience with the use of biologics during gestation is extremely lacking because of the observational nature of the available studies and the difficulty in designing proper clinical trials in pregnancy. Among the studied biologics, more information was published on TNFα inhibitors and, in particular, on their potential passage through the placenta and impact on the fetus. Currently, a fragment of anti-TNFα monoclonal IgG, certolizumab pegol, is considered safe with almost no placental transfer. Subsequent observations are suggesting a comparable safety for the soluble TNFα receptor etanercept. Another biologic, eculizumab, the anti-C5a antibody used to treat complement-mediated microangiopathies, is also considered safe due to the unique engineered IgG2/4κ formulation that limits its passage through the placental barrier. Still, long-term data about children born to women treated with biologics in pregnancy are not attainable. Data on breastfeeding are currently available for several biologics. This article reviews the literature available about which drugs are considered safe during pregnancy and lactation, which are not, and on future prospects.