Antinuclear Antibodies Research Articles

P41 Decoding short stature in a child with lupus nephritis: an unusual association with de la Chapelle syndrome

Abstract Introduction Recent studies have implicated the dysregulation of epigenetic factors in maintaining favourable lyonization of X-chromosome as a plausible putative mechanism in causing high incidence of systemic lupus erythematosus (SLE) in females. This is reflected by the increased risk of SLE in patients with ‘disorders of sex development’ (DSD) such as Klinefelter’s syndrome (47,XXY). de la Chapelle syndrome (46,XX with SRY gene) is another DSD wherein patients resemble males phenotypically with 2 X-chromosomes in their karyotype. Herein, we report the diagnostic and therapeutic challenges in a case of juvenile-onset SLE with refractory lupus nephritis and concomitant association of de la Chapelle syndrome. Case description A 13-year-old boy presented with history of chronic febrile inflammatory polyarthritis involving small and large joints for 6-months. On examination, he had short stature, and swelling, tenderness and restriction of movement of the proximal and distal interphalangeal joints, wrist and shoulder joints of both sides. Investigations revealed elevated erythrocyte sedimentation rate with normal C-reactive protein. Routine urine microscopy examination was suggestive of proteinuria. Further immunological investigations revealed hypocomplementemia, positive anti-nuclear antibody (4+, homogeneous pattern) and elevated titres of anti-double stranded DNA. He was also noted to have positive direct coomb’s test and antiphospholipid antibodies. His renal biopsy was suggestive of lupus nephritis (Class II). Based on the above constellation of clinical and laboratory parameters, a diagnosis of SLE with lupus nephritis (Class II) and musculoskeletal involvement was proffered. He was started on oral prednisolone (2 mg/kg/day followed by taper), hydroxychloroquine (5 mg/kg/day) and sun protective measures. However, persistence of proteinuria after 3-months necessitated addition of mycophenolate mofetil (1200 mg/m2/day) following which his SLE-disease activity went into remission. Notwithstanding the control of SLE-disease activity, there was no improvement in his height after 1-year of follow-up. A pediatric endocrinology consultation for short stature revealed features of idiopathic growth hormone (GH) deficiency and primary hypogonadism. Chromosomal analysis was suggestive of 46,XX karyotype, and fluorescence in situ hybridisation revealed ‘XX’ pattern with SRY gene located on one of the X chromosomes. He was commenced on recombinant GH therapy for 18-months following which his height improved. At 2-years of follow-up, he developed worsening proteinuria. A repeat renal biopsy was suggestive of class-IV lupus nephritis. However, he responded poorly to 6-doses of monthly intravenous cyclophosphamide (500 mg/m2/dose). Considering refractory lupus nephritis, he was commenced on rituximab [(375 mg/m2/dose) at 0 and 2-weeks] following which his proteinuria became passive. He remains well on follow-up. Discussion SLE in DSD has been more frequently described in the context of Klinefelter’s syndrome (47, XXY), implicating the X chromosome as a putative mechanism in its pathogenesis. However, the clinical profile and outcome of SLE in patients with de la Chapelle syndrome has not been explored extensively. de la Chapelle syndrome (46, XX with SRY gene), first described in 1964, is a rare DSD with a reported prevalence of 1/20000 to 1/25000 newborn males. The clinical phenotype includes decreased body height, gynecomastia, maldescended testis and other features of hypogonadism including infertility. Chagnon et al reported the first patient of SLE in de la Chapelle syndrome. Authors described a 19-year-old man who presented with features of SLE since early childhood. His disease was complicated by severe rash, mucositis, arthritis, focal proliferative glomerulonephritis, transaminitis and refractory thrombotic thrombocytopenic purpura, and osteoporosis (including growth failure). In addition, he also had primary hypogonadism with normal GH. Dillon et al also reported another 46, XX male with presence of SRY gene. However, the clinical details including treatment were not elucidated in this paper. Both these patients were phenotypically male due to the presence of SRY gene, similar to the index patient. Our patient’s difficult clinical course with arthritis, growth failure and refractory lupus nephritis, and primary hypogonadism was similar to the patient reported by Chagnon et al. The treatment protocol of SLE in DSD is not well-established. Chagnon et al reported using corticosteroids, hydroxychloroquine, methotrexate, intravenous pulse cyclophosphamide, azathioprine, and plasmapheresis. The index patient was treated similarly; however, due to refractory lupus nephritis, he was also given rituximab. To the best of our knowledge, this is the first report of successful use of anti-CD20 therapy in SLE with DSD such as de la Chapelle syndrome. Key learning points • This case highlights the challenges in diagnosis and management of patients with DSD including de la Chapelle syndrome. The main learning point from this case was that short stature in juvenile-onset SLE in a boy with features of primary hypogonadism warrants further evaluation. As reported in previous literature, this subset of patients may not respond adequately to conventional first-line therapy. The need for escalation of therapy or primary therapy with rituximab in such patients needs further exploration. Another point of concern is using cyclophosphamide, a known drug to have adverse effect on testes, in these patients since it may further compromise testicular function.

The presence of antinuclear antibodies does not affect the euploidy rate in patients undergoing PGT-A: a retrospective single-center study

The presence of antinuclear antibodies does not affect the euploidy rate in patients undergoing PGT-A: a retrospective single-center study

HLA-DRB1*01 predicts treatment outcome in juvenile idiopathic arthritis: A retrospective-prospective cohort study.

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.

Circulating Autoantibodies in Adults with Hashimoto's Thyroiditis: New Insights from a Single-Center, Cross-Sectional Study.

Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. A cross-sectional study was conducted at the University Hospital "R. Dulbecco" in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

Eosinophilic cationic protein and D-Dimer are potential biomarkers to predict response to antihistamines but not to omalizumab in chronic spontaneous urticaria

ABSTRACT Introduction: Biomarkers that could reliably anticipate the effectiveness of antihistamines and omalizumab in treating chronic spontaneous urticaria (CSU) have not been conclusively identified. Our objective was to examine how eosinophilic cationic protein (ECP), tryptase, D-dimer, and total Immunoglobulin E (IgE) impact the response to antihistamine and omalizumab treatments in individuals with CSU. Methods: In this cross-sectional retrospective study, CSU patients that had undergone treatment with either antihistamines or omalizumab for a minimum of 12 weeks between 2015 and 2021 at an Allergy and Immunology Department were analyzed. Several demographic and laboratory parameters including eosinophil counts, mean platelet volüme (MPV), sedimentation, C-reactive protein (CRP), antinuclear antibodies (ANA) and Anti-thyroperoxidase (Anti-TPO) and total IgE, tryptase, ECP and D-dimer were retrived from patient files. The association of these biomarkers with Urticaria Control Test (UCT) and the effect of these biomarkers on treatment response were evaluated. Treatment response was assessed using the UCT, with a score of UCT ≥ 12 indicating a responder and UCT < 12 indicating a non responder. Results: The patients in the omalizumab group were older, had a longer disease duration and had worse urticaria control (lower baseline UCT scores). 421 patients were treated with antihistamines and 88 patients were treated with omalizumab. ECP was found to be inversely correlated with baseline UCT (p < 0.001 r=−0.268). ECP and D-dimer levels of non-responder patients in the antihistamine group were significantly higher than in responder patients (ECP: 49 ng/mL vs 28.1 ng/mL, p < 0.001) (D-dimer: 0.60 mg/L vs 0.30 mg/L, p < 0.001), while there were no significant difference in terms of tryptase and total IgE. These four biomarkers were similar, in omalizumab responders and non responders. Conclusion: In this study with CSU, we looked at predictors of responses to treatments. ECP can serve as a marker of poor urticaria control and may predict antihistamine refractoriness along with D-dimer.

Clinical Characteristics of Anti-Synthetase Syndrome: Analysis from the CLASS project.

Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD. We utilized a large, international, multi-center "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort. Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD. We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD.

Different antinuclear antibody subgroups of anti-melanoma differentiation-associated gene 5-positive dermatomyositis had variability in clinical presentation: a multicentre retrospective cohort study

IntroductionThis study aimed to investigate the association between ANA and clinical characteristics as well as prognosis in a cohort of patients with anti-MDA5+ DM.Material and methodsWe conducted a systematic retrospective study of medical records from Nanjing Medical University myositis associated interstitial lung disease (ILD) contort.ResultsA total of 246 patients with anti-MDA5+ DM were enrolled in this study, with 28.5% males and 71.5% females. The median age was 53.0 years, the median disease duration was 2 months, and the median follow-up period was 12.0 months. ANA positivity rate at baseline was 52.4% in anti-MDA5+ DM patients. The ANA-positive group showed significantly higher positivity rates of anti-Ro52 antibodies (72.9% vs 54.7%, p=0.003) and anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies (9.3% vs 2.6%, p=0.033) compared to the ANA-negative group, but lower ALT levels [39.0 (21.5, 79.3) vs 51.3 (36.5, 95.8), p=0.006].In a subgroup analysis of the ANA-positive group, MDA5+++ patients had a higher incidence of RPILD compared to the MDA5+ group (P=0.028). In the ANA negative subgroup analysis, MDA5+++ patients had a higher mortality rate and worse prognosis compared to the MDA5+ group (P=0.026). Multivariate COX regression analysis showed that elevated LDH levels and the presence of rapidly progressive interstitial lung disease (RPILD) were associated with poor prognosis in ANA-negative anti-MDA5+ DM patients [hazard ratios of 1.002 (95% CI 1.001, 1.003, P = 0.020) and 13.694 (95% CI 15.032, 37.267, P &lt; 0.001), respectively].ConclusionsANA is frequently found in patients with anti-MDA5+ DM. High titres of anti-MDA5 antibodies are associated with mortality and RPILD.

Clinical characteristics, treatment and outcome of subacute cutaneous lupus erythematosus induced by PD-1/PD-L1 inhibitors.

PD-1/PD-L1 inhibitors have increasingly been associated with the occurrence of subacute cutaneous lupus erythematosus (SCLE), but the clinical characteristics and outcomes remain under-explored. Literature on PD-1/PD-L1 inhibitors induced SCLE was retrieved from Chinese and English databases until June 31, 2024, and clinical data of patients were extracted for retrospective analysis. Twenty-nine patients participated, with a median age of 63 years (range 43, 80). The most frequently reported drugs were Nivolumab (51.7%) and pembrolizumab (31.0%). The median time from treatment initiation to SCLE onset was 3 months (range 0.5, 47). Cutaneous manifestations presented primarily as papulosquamous lesions (65.5%) and erythema annulare (31.0%), predominantly occurring on the trunk (51.7%) and arms (51.7%). Serological analysis revealed positive anti-Ro antibodies in 91.7% of patients, positive antinuclear antibodies in 75.0%, and positive anti-La antibodies in 50.0%. Skin biopsies showed interface dermatitis in 65.5% of cases and lymphocyte infiltration in 82.8%. Treatment with topical corticosteroids, systemic corticosteroids, and hydroxychloroquine led to gradual improvement or resolution of the rash, with a median recovery time of 1 month (range 0.5, 11). As the use of PD-1/PD-L1 inhibitors in oncology increases, SCLE should be recognized as a rare cutaneous adverse effect. Histological and serological evaluations play a critical role in diagnosing SCLE. Typically, SCLE resolves on its own with appropriate local and systemic treatment.

Extra-Hepatic Portal Venous Obstruction in Pregnant Women of South-Asian Descent: A Case Series

Liver diseases complicate approximately 3% of pregnancies worldwide, and require specialized care to ensure optimal pregnancy outcomes. Extra-hepatic portal venous obstruction (EHPVO), even though asymptomatic in a majority of the cases, has a higher risk of variceal bleeding in pregnancy and adverse pregnancy outcomes. In this series, we describe five cases of EHPVO presenting during pregnancy at our tertiary care hospital, their antenatal management, and delivery outcomes. In our case series on EHPVO in pregnancy, a majority of the women were diagnosed during childhood and adequately asymptomatic before pregnancy. Two women underwent Endoscopic band ligation for esophageal varices and one woman underwent splenectomy before pregnancy for disease control. One woman was Anti-nuclear antibody (ANA) positive and another was Anti-phospholipid antibody (APLA) positive, while the other three did not have pre-existing thrombotic tendencies. One patient required Endoscopic band ligation during pregnancy. Pregnancy complicated by hypertension was noted in two of the five women (40%). Four of the five women (80%) had thrombocytopenia requiring blood products during delivery. Two women underwent preterm vaginal delivery, and one woman underwent preterm Caesarean section because of placental abruption. Three women had a post-partum hemorrhage, which was effectively managed with uterotonics and blood products. All five women and their neonates were discharged in good health. Multi-disciplinary approach with standardized antenatal care can give positive pregnancy outcomes in women with EHPVO.

Клинико-эпидемиологические особенности системной красной волчанки у детей: данные наблюдений ГБУЗ “Морозовская ДГКБ ДЗМ”

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown etiology characterized by hyperproduction of autoantibodies. The problems of timely diagnosis and identification of predictors of an unfavorable outcome of SLE are relevant due to the variable clinical picture and a high risk of 5-year mortality in the absence of treatment. The purposes of this research were to assess the frequency of various variants of SLE onset, to identify trigger factors contributing to the development of the disease and to analyze the degree of disease activity in children. Materials and methods used: a single-center cohort retrospective study was conducted involving patients aged 9 to 17 y/o who had undergone inpatient treatment at the rheumatological department of the Morozov Children’s City Clinical Hospital (Moscow, Russia) in 2020-2023, specifying age, gender, assessing the frequency of observed symptoms of SLE onset, disease activity according to the SLEDAI scale, laboratory parameters and drug treatment. Results: total of 45 records were analyzed: 75.5% (34) girls/24.5% (11) boys; median age 15 [13; 15] y/o; most frequent clinical syndrome was cutaneous (75.5%); kidney damage was noted in 40% of cases. 86.6% had hematological disorders as follows: thrombocytopenia and leukopenia (48.9%), anemia (46.6%): Coombs-positive anemia (71.4%), lymphopenia (37.7%) and increased ESR (66.6%). Antinuclear factor (ANF Hep2) was detected in all cases. According to the SLEDAI-2K scale, the median disease activity was 11 [7; 16] points. Low disease activity (less than 6 points) was observed in 4.4% (2), average (6 to 10 points) in 44.4% (20), high (11 to 19 points) in 37.7% (17), above average (over 20 points) in 13.3% (6). Moreover, disease activity was higher in girls (p=0.940) and a relationship was found between the time required for diagnosis and disease activity according to the SLEDAI-2K scale (p=0.206). Drug therapy: glucocorticoids (GCS) orally in all cases, intravenous pulse GCS therapy in 71.0%. Hydroxychloroquine therapy was prescribed in 100.0%, mycophenolate mofetil in 57.7%, intravenous immunoglobulin in 37.7%, cyclophosphamide in 13.3%, methotrexate in 6.6%, biological therapy in 31.0%, the drug of choice was rituximab. Conclusion: updating the data on the frequency of various variants of SLE debut as well as identifying the new trigger factors contributing to the development of the disease are necessary steps aiming to increasing the awareness of the SLE course with its debut in childhood, optimizing the diagnosis process and reducing the risk for complications.

18F-FDG PET/CT in the Evaluation of Polyarteritis Nodosa.

A 61-year-old man with a medical history of human immunodeficiency virus well controlled on antiretroviral therapy presented for distal sensorimotor symptoms, fatigue, and recurrent fevers. Erythrocyte sedimentation rate and C-reactive protein were both elevated. Antineutrophilic cytoplasmic antibody and antinuclear antibodies were negative. Neurologic imaging workup was unremarkable. 18F-FDG PET/CT, which was crucial for diagnosis, demonstrated pathological tracer activity throughout the medium-sized vessels with sparing of the aorta. In view of presentation, comorbidities, and imaging findings, polyarteritis nodosa was diagnosed. The patient was treated appropriately with steroids and cyclophosphamide with significant symptomatic improvement.

Autoantibody against aquaporin-5 may be a new diagnostic biomarker for primary Sjögren's syndrome.

The study aims to assess the diagnostic and clinical significance of autoantibodies against aquaporin-1 (anti-AQP1) and aquaporin-5 (anti-AQP5) in primary Sjögren's syndrome (pSS). A total of 163 participants were categorized into three groups: pSS group, other connective tissue diseases (CTD) group, and healthy control (HC) group. The levels of anti-AQP1 and anti-AQP5 autoantibodies in serum were determined using enzyme-linked immunosorbent assay (ELISA), and clinical data from patients were collected for statistical analysis. Our results showed that the level of anti-AQP1 in the pSS group was higher than in the HC group (P < 0.05), and no significant difference was observed between the pSS group and the CTD group (P > 0.05). ROC showed that the anti-AQP1 had no diagnostic value for pSS (P > 0.05). The anti-AQP5 level of 39 healthy adults was all below the cut-off value (14.10ng/ml) (P < 0.05). The level of anti-AQP5 in the pSS group was higher than the CTD group (P < 0.05), the AUC was 0.86 (95% CI 0.80-0.93), with a sensitivity of 0.95 (95% CI 0.87-0.99) and a specificity of 0.70 (95% CI 0.58-0.84). No correlation was found between anti-AQP5 levels and the EULAR primary Sjögren's syndrome disease activity index score, anti-SSA, anti-SSB, antinuclear antibodies, rheumatoid factor, anti-ds-DNA, salivary gland flow rate, complement 3, and lymphocyte count in pSS samples (P > 0.05), respectively. Therefore, the elevated anti-AQP5 may emerge as a novel diagnostic biomarker for pSS patients due to high sensitivity and specificity.

Clinical relevance and frequency of cytoplasmic patterns observed in ANA-Hep-2: experience of Cairo University Hospitals.

Antinuclear antibodies (ANA) are the most common biomarkers observed in autoimmune diseases. Cytoplasmic staining patterns on ANA-Hep-2 are gaining recognition but with scanty information about their clinical and diagnostic role. The aim is to assess the frequency of cytoplasmic ANA patterns in autoimmune diseases, and to evaluate their possible associations with clinical diagnoses and autoantibodies. This observational cross-sectional study was conducted by examining and/or reviewing ANA by indirect immunofluorescence assay during a 13-month period. This was followed by testing the group of patients with a positive cytoplasmic staining pattern (n = 92) using the Microblot-Array ANA plus for the presence of 44 specific autoantibodies. Out of 2741 samples, 1791 (65.3%) tested negative, 845 (30.9%) tested positive nuclear staining patterns, 56 (2.0%) positive solitary cytoplasmic staining patterns, and 49 (1.8%) positive mixed nuclear and cytoplasmic patterns. Ninety-two cases (3.4% of the total cases) were analyzed using Microblot-Array ANA plus, with reticular as the most frequent cytoplasmic pattern, followed by dense fine speckled. The most frequently associated disease with reticular pattern was primary biliary cholangitis (28.9%), and the most frequently detected autoantibodies were against M2 (66.7%). The most frequently associated disease with dense fine speckled pattern was systemic lupus erythematosus (69.4%), and the most frequently detected autoantibodies were against nucleosome (57.7%) and ribosomal P0 (53.8%). This study highlights the significance of reporting cytoplasmic staining patterns and their importance in assessment of autoimmune diseases. Larger cohort studies on treatment naïve patients are recommended.

Systemic sclerosis-associated interstitial lung disease: How to manage in 2024?

Systemic sclerosis (SSc) or scleroderma is an autoimmune disease characterized by immune dysregulation which leads to progressive fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is present in approximately 65% of patients with SSc and it accounts for approximately 40% of all SSc deaths. Risk factors associated with the development of systemic sclerosis related interstitial lung disease (SSc-ILD) include male sex, African heritage, high modified Rodnan skin score (mRSS), presence of anti-Scl-70/Topoisomerase I antibodies, and nucleolar pattern on antinuclear antibody (ANA). The primary tool to diagnose ILD in patients with SSc is high-resolution computed tomography (HRCT). Full pulmonary function tests (PFTs) with diffusing capacity of the lungs for carbon monoxide (DLco) and ambulatory desaturation testing should be obtained following the diagnosis of SSc-ILD for disease monitoring. The purpose of this review is to provide an updated guide for the management of SSc-ILD. Our proposed first line treatment for SSc-ILD is immunosuppressive therapy such as mycophenolate mofetil, tocilizumab, and rituximab which are discussed in depth, and we present the evidence-based data that has justified the use of these pharmacotherapies. Other immunosuppressive treatments are also reviewed, and we discuss the role of antifibrotic therapy. Finally, we dive into other avenues of treatments such as chimeric antigen receptor (CAR)-T cell therapy and hematopoietic stem cell transplant.

Clinical and immunologic abnormalities in COVID-19

Objective: to find approaches to improve diagnostics of the debut of rheumatic manifestations, associated with COVID-19.Material and methods. Data from 1000 patients from the COVID-19 registry were included in the prospective cohort study. In all patients, the diagnosis of COVID-19 was confirmed by polymerase chain reaction. Of these patients, 380 (41.8% men and 58.2% women, mean age 47.0±2.5 years) had rheumatic manifestations. Patients were examined using routine clinical methods. Immunological markers of rheumatic diseases were determined, including antibodies against cyclic citrullinated peptide, rheumatoid factor, antiphospholipid antibodies and antinuclear factor (ANF), and an immunoblot for antinuclear antibodies was performed if ANF titer was &gt;1:160.Results and discussion. Patients had the following rheumatic manifestations: arthralgias (in 342), myalgias (in 23), skin rashes (in 15). ANF titers &gt;1:160 were found in 57.6% of patients. No reliable data indicating the development of an antiphospholipid syndrome were found in the study group. Lupus anticoagulant was detected in 5.7% of cases, antibodies against β2-glycoprotein in 5.7%, antibodies against cardiolipin in 3.8%. High ANF titers were found in 63.9% of patients with arthralgia. Gender-specific differences were found when analyzing the correlation between ANF titers and rheumatic manifestations: in men, high ANF tires were associated with myalgias, and in women with arthralgias. The presence of rheumatic manifestations depended directly on the severity of the disease. A correlation between arthralgia and leucopenia was also found – leucocyte count &lt; 3,9 ‧109 /L was a predictor of arthralgias. The sensitivity and specificity of the model were 99.3 and 91.2%, respectively.Conclusion. The results suggest that COVID-19 can provoke the development of immunological abnormalities that may subsequently lead to the development of an autoimmune diseases (AID). The optimal approach to prevention and early detection of AID in patients with coronavirus infection caused by SARS-CoV-2 is to monitor laboratory parameters – leukocyte count and CRP level. If rheumatic manifestations are present, the use of immunological and imaging examinations is also recommended.

Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort

BackgroundThere is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden.MethodsAutoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000–2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models.ResultsDuring the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13–7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76–15.65) and hypothyroidism (HR 3.74, 95% CI 1.14–12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64–23.55) for ANA positive individuals.ConclusionsIndividuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up.

ANA-positive versus ANA-negative Antiphospholipid Antibody-positive Patients: Results from the APS ACTION Clinical Database and Repository.

This study focused on the prevalence and impact of antinuclear antibodies (ANA) in antiphospholipid antibody (aPL)-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs). Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the APS ACTION Registry. Patients with concomitant SARDs were excluded. 430 aPL-positive patients were included in the analysis, 56% ANA-positive and 44% negative. ANA positivity was significantly associated with history of hematologic manifestations (persistent autoimmune hemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA-positive vs 7% of ANA-negative, p= 0.006). Triple aPL-positivity was more frequent in the ANA-positive subgroup (p= 0.02), along with low baseline C3 and C4 levels (p= 0.05 and p= 0.009, respectively), and higher frequency for extractable nuclear antigens (ENA). Among aPL-positive patients with no APS classification, ANA-positive patients showed a higher rate of arthritis (p= 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA-positive and 96 were ANA-negative; ANA-negative patients had a higher number of pregnancies (p= 0.018), and number of live births (p= 0.014). A wider proportion of ANA-positive patients were treated with hydroxychloroquine (HCQ) (p< 0.001). When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA-positive patients showed higher rates of systemic autoimmune features, including hematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA-negative had a higher rate of pregnancies and live births.

Peripheral Ischemia and Necrosis Revealing Buerger&amp;apos;s Disease in an Internal Medicine Department

Buerger&amp;apos;s disease is a systemic vasculitis strongly correlated with tobacco use. It entails a heavy socio-occupational impact. We report the case of a 26-year-old patient with ischemia of the lower limbs revealing Buerger’s disease. He is known smoker with passive exposure to Indian hemp. He was seen for ischemic foot pain that had been progressing for a year. Involvement began in the left big toe. Subsequently, hyperalgesic necrotic lesions were observed on the 3rd, 4th and 5th toes of the foot. Biological investigations revealed an inflammatory syndrome with normocytic anemia and increased C-reactive protein. Retroviral, syphilitic, Hepatitis B and C viruses and SARS-CoV-2 serologies were negative. Antinuclear antibodies were initially borderline at 100 IU with speckled fluorescence, then negative on control. Neutrophil cytoplasmic antibodies and antiphospholipid antibodies were negative. Investigation of thrombophilia was non-contributory, notably factor V mutation testing, antithrombin III assay, proteins C and S and fibrinogen. An arterial ultrasound revealed extensive arterial thrombosis with thickening of the femoral arterial vessel walls. Thromboangiitis obliterans was confirmed and the patient was put on corticosteroids and adjuvant therapy. Surgical treatment was performed 4 months later. Buerger&amp;apos;s disease is a serious vascular disorder which must be diagnosed very early in order to prevent complications. Early smoking cessation leads to remission in the early phase.

A Clinical Evaluation of the Role of Autoimmunity in the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis.

Background/objectives: Both erosions and osteoporosis in rheumatoid arthritis (RA) have common mechanisms. The aim of this study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity. Methods: Patients fulfilling the ACR 1987- or ACR/EULAR 2010-criteriae for RA. performed radiographs (erosions evaluated by the modified Sharp/van der Heidje erosion score) and biology for anti-citrullinated peptide antibodies (ACPAs), rheumatoid factors (RFs) and anti-nuclear antibodies (ANAs) at intervals of less than 2 years from dual-energy X-ray absorptiometry (DXA) for BMD assessment. Results: A total of 149 patients were included, (75.8% women, mean age of 62 y.o (SD 9.61) and a median disease duration of 132 months [60; 240]). A total of 61.1% patients were ACPA positive, 79.9% were erosive and 10.7% had a hip or spine T-score ≤ -2.5. A higher erosion score was associated with a lower BMD (value: -0.222; p = 0.009) and T-score (value -0.397; p < 0.0001) in the hip. ACPA status was associated with a higher erosion score (63.0 (53.2) vs. 45.5 (44.1) for ACPA- (p = 0.04)). ACPA titers were associated with a lower BMD in the hip (value -0.216; p = 0.01). In linear regression, erosion and BMD were still associated, but this association is not driven by ACPA status or titer. Conclusions: In RA patients, erosions and BMD are inversely associated but this relationship does not seem to be driven by autoimmunity only. However, the presence of ACPA or erosion should lead to osteoporosis screening.

Mitigating overuse of antinuclear antibody (ANA) testing through educational intervention: a study in internal medicine and neurology departments.

Overuse of antinuclear antibody (ANA) tests leads to increased costs, false positives, and unnecessary treatments. This study evaluated ANA overuse in internal medicine and neurology departments and assessed the impact of an educational intervention. This quality improvement educational intervention study examined ANA test overuse in five internal medicine departments and one neurology department at a university-affiliated medical center. The educational intervention included a session focusing on ANA testing appropriateness. Outcome measures comprised the ANA/new patient ratio (APR) and the percentage of positive ANA test results. Outcomes were compared between the pre- and post-intervention periods (both 6months). The intervention took place in December 2021. The APR decreased from 43% in the pre-educational intervention period to 27% in the post-intervention period in the neurology department (odds ratio [OR] 0.49, confidence interval [95% CI] 0.37-0.63, P < 0.0001) and from 2.6% to 2.2% in the internal medicine departments (OR 0.89, 95% CI 0.73-1.10, P = 0.28). The percentage of positive ANA tests increased from 43% pre-intervention to 53% in the post-intervention period (OR 1.49, 95% CI 0.90-2.46, P = 0.12) in the neurology department and from 48% to 59% (OR 1.56, 95% CI 0.99-2.44, P = 0.0543) in the internal medicine departments. A simple educational intervention reduced unnecessary ANA testing in the neurology department but not in internal medicine departments, improving patient selection and potential cost savings. The results underscore the importance of targeted education to promote evidence-based behavior among healthcare professionals. Further research with longer follow-up is needed to assess the sustainability of these improvements.