Positive Antinuclear Antibody Research Articles

The Diagnostic Role of Antinuclear Antibody: A Study of Clinical Utility in a Tertiary Hospital

Abstract Introduction: Various studies reported unnecessary and inappropriate serology testing of rheumatic diseases leading to a significant waste in healthcare utilization. The purpose of this study is to evaluate the clinical utility of antinuclear antibody (ANA) testing in a real-world setting within a tertiary hospital for systemic lupus erythematosus (SLE) and other ANA-associated rheumatic diseases (AARDs), as well as to identify patient characteristics and test results that predict rheumatic disease association. Subjects and Methods: This is a retrospective study of patients aged 15 years or older who underwent ANA testing at Aseer Central Hospital from January 2018 to December 2022. Data collected included patient demographics, clinical presentations, referral physician type, ANA test results, and final diagnoses. Descriptive statistics characterized patient demographics and ANA test results. Sensitivity, specificity, and predictive values of ANA testing were calculated for SLE and AARD diagnoses. Chi-squared test was used to identify the predictive values of AARDs. Results: Of the 2141 patients tested for ANA at Aseer Central Hospital, 583 (27.2%) tested positive, with a higher proportion of females (80.8%). Notably, 85.1% of patients who tested ANA positive were under 55 years old. The highest ANA test-positive proportion was noticed by rheumatologist physician’s referral (67.6%), referral symptoms including joint symptoms (38.3%), mucocutaneous symptoms (19.7%), renal disease symptoms (14.4%), and hematological abnormalities (14.2%). The sensitivity and specificity of ANA for diagnosing SLE were 86.4% and 79.3%, respectively, with a positive predictive value (PPV) of 31.7% and a negative predictive value (NPV) of 98.1%. The sensitivity and specificity of other AARDs were 85.4% and 73.9%, respectively, with a PPV of 6% and an NPV of 99.6%. Significant associated factors with AARDs included younger age (<55 years), female patients, higher ANA titer, rheumatologist referral, and clinical indications such as sicca symptoms, myopathy, mucocutaneous symptoms, and hematological abnormalities (P < 0.001). Conclusion: In this study, ANA testing showed a good sensitivity and NPV in ruling out AARDs; however, its poor specificity and PPV suggest that positive ANA findings should be interpreted cautiously. Younger age, female gender, higher ANA titer, rheumatologist referral, and specific clinical indications were significantly associated with AARDs, suggesting the importance of targeted ANA testing in clinical practice.

Genetic analysis of asymptomatic antinuclear antibody production.

Antinuclear antibodies (ANA) are detected in up to 14% of the population and the majority of individuals with ANA are asymptomatic. The literature on the genetic contribution to asymptomatic ANA positivity in the population is limited. In this study, we aimed to perform a multi-ancestry genome-wide association study (GWAS) of asymptomatic ANA positivity. Asymptomatic ANA positive and negative individuals from the All of Us Research Program were included in this study, selecting those with an ANA test by immunofluorescence and no evidence of autoimmune disease. Imputation was performed and a multi-ancestry meta-analysis including approximately 6 million single-nucleotide polymorphisms (SNPs) was conducted. Genome-wide SNP based heritability was estimated using the GCTA software. A cumulative genetic risk score for lupus was constructed using previously reported genome-wide significant loci. 1,955 asymptomatic ANA positive and 3,634 asymptomatic ANA negative individuals were included across three genetic ancestries. The multi-ancestry meta-analysis revealed SNPs with a suggestive association (p-value < 1×10 -5 ) across 8 different loci, but no genome-wide significant loci were identified. A gene variant upstream of HLA-DQB1 (rs17211748, P = 1.4×10 -6 , OR = 0.82, 95% CI 0.76-0.89) showed the most significant association. The heritability of asymptomatic ANA positivity was estimated to be 24.9%. Asymptomatic ANA positive individuals did not exhibit increased cumulative genetic risk for lupus compared to ANA negative individuals. ANA production is not associated with significant genetic risk and is primarily determined by non-genetic, likely environmental, factors.

A proposed clinical tool to identify high-risk patients for monogenic lupus: a pilot study.

To develop an easy-to-use and efficient clinical score to identify monogenic lupus based on clinical presentations and to stratify patients who may benefit from confirmatory molecular genetic testing. A comprehensive literature review identified 55 distinct items across 12 clinical and laboratory domains, narrowed down to the top ten by a panel of 12 expert paediatric rheumatologists with 80% consensus. The proposed score was tested in a pilot study on 10 patients with monogenic lupus and 30 control subjects with various autoimmune and autoinflammatory diseases. All patients, both with monogenic lupus and the control group, were then scored, and a receiver operating characteristic curve was employed to determine the threshold that distinguishes monogenic lupus from non-monogenic lupus. The clinical score comprised 10 items. Among all patients, the most frequent items were antinuclear antibody positivity and consanguinity, followed by early disease onset (<5 years), with no significant differences between monogenic lupus patients and the controls. However, the monogenic lupus patients exhibited significantly higher rates of family history of lupus, failure to thrive, cutaneous lesions, brain imaging changes, a low C1q level, and recurrent infections. Also, they achieved the highest scores compared to the controls. A score of more than three was found to be highly predictive for diagnosing monogenic lupus, with a sensitivity of 90% and a specificity of 90%. Our clinical score appears to be a valuable tool for the early identification of patients with monogenic lupus who may require further molecular genetic testing for confirmation.

Genetic association of antinuclear antibodies with HLA in JIA patients: a Swedish cohort study

BackgroundJuvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition.MethodsWe analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm.ResultsCase–control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to HLA-DQA1 and HLA-DRB1. HLA-DRB1*08:01, HLA-DQA1*04:01, and HLA-DQB1*04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the HLA-DRB1-DQA1-DQB1 haplotype, our analysis suggests that HLA-DRB1*08 might be the primary allele linked to JIA susceptibility. The HLA-DRB1*11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the HLA-DRB1-DQA1-DQB1 haplotype, HLA-DRB1*11, and HLA-DPB1*02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity.ConclusionsThis study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.

Association between Epstein-Barr virus infection and serum positivity rate of anti-nuclear antibodies in Chongqing, China: A cross-sectional observational study.

Epstein-Barr virus (EBV) infects over 95% of the global population and is strongly associated with various autoimmune diseases. Anti-nuclear antibodies (ANA) serve as valuable laboratory biomarkers for screening and supporting the diagnosis of various autoimmune diseases. The aim of this study was to assess the prevalence of EBV infection and its association with ANA. This retrospective study employed standard indirect immunofluorescence assay to determine ANA levels, EBV-specific immunofluorescence assay, or plasma EBV-DNA testing. Demographic data including gender and age were collected to observe variations in EBV infection status and ANA positivity rates among different populations. Incorporating 6492 hospitalized patients who underwent ANA antibody spectrum testing, it was observed that serum positivity rates gradually increased with age. The overall serum positivity rate of ANA in females (25.14%) was significantly higher than that in males (13.76%). Among hospitalized patients undergoing EBV-DNA testing, adults aged 21 to 40 years were least affected by EBV, with a positivity rate of 11.96%; however, as age increased, the positivity rate gradually increased. Among the 5225 patients undergoing EBV antibody spectrum testing, ANA-positive patients exhibited significantly higher serum positivity rates for Epstein-Barr nuclear antigen 1 immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin A, and Epstein-Barr virus viral capsid antigen immunoglobulin A antibodies compared to ANA-negative patients (P < .001; P < .001; P = .013; P < .001). The EBV-DNA positivity rate in ANA-positive patients was also significantly higher than in ANA-negative patients, yielding the same conclusion (P = .012). The positivity rates of ANA antibodies in patients with past EBV infection and reactivation were significantly higher than those in uninfected patients (P < .001; P = .006). The positivity rate of ANA antibodies in reactivated patients was significantly higher than that in primary infected patients and those with past infections (P < .001; P < .001). Among ANA-positive patients, the positivity rates of EBV antibody spectrum and EBV-DNA were higher compared to ANA-negative patients. The positivity rates of ANA in patients with past EBV infection and reactivation were higher than those in uninfected patients.

Changes of cerebral structure and perfusion in subtypes of systemic sclerosis: a brain magnetic resonance imaging study.

The characteristics of brain impairment in different subtypes of systemic sclerosis (SSc) (dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc) remain unclear. This study aimed to characterize cerebral structure and perfusion changes in different subtype of SSc patients using magnetic resonance (MR) imaging. Seventy SSc patients (46.0 ± 11.7 years, 62 females) and 30 healthy volunteers (44.8 ± 13.7 years, 24 females) were recruited and underwent brain MR imaging and Montreal Cognitive Assessment (MoCA) test. Gray matter (GM) volumes were measured using voxel-based morphometry analysis on T1-weighted images. Voxel-based and regional cerebral blood flow (CBF) was calculated on arterial spin labelling images. The cerebral structural and perfusion measurements by MR imaging were compared among dcSSc, lcSSc and healthy subjects using one-way ANOVA. The correlations between clinical characteristics and MR imaging measurements were also analyzed. The dcSSc patients exhibited a significant reduction in GM volume in the para-hippocampal region (cluster p < 0.01, FWE corrected) compared with healthy volunteers. Whereas, SSc patients, particularly lcSSc patients, showed elevated CBF in cerebellum, insula, cerebral cortex, and subcortical structures (regional analyses: all p < 0.05; voxel-based analyses: cluster p < 0.01, FWE corrected). Furthermore, clinical characteristics of modified Rodnan skin score (mRSS) (r value ranged from -0.29 to -0.45), MoCA scores (r = 0.40) and antinuclear antibody (ANA) positivity (r=-0.33) were significantly associated with CBF in some regions (all p < 0.05). The manifestations of brain involvement vary among different subtypes of SSc. In addition, severe skin sclerosis may indicate higher risk of brain involvement in SSc patients.

Earlier vs. later time period of COVID-19 infection and emergent autoimmune signs, symptoms, and serologies

ObjectiveAutoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities. MethodsPatients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry. We assessed relationships between symptoms, serologies, and immunophenotypes in earlier (3/1/2020-1/31/2021) vs. later (2/1/2021-8/15/2022) periods, with different predominating SARS-CoV-2 viruses. Results57 subjects had earlier and 23 had later pandemic COVID-19. 35 % of earlier vs. 17 % of later pandemic patients had CTD symptoms (p 0.18). More patients were antinuclear antibody (ANA) positive (44 % vs. 13 %, p 0.01) and had lupus anticoagulant (11 % vs. 4 %, p 0.67). After adjustment for age, race, and sex, earlier (vs. later) COVID-19 was associated with increased ANA positivity (OR 4.60, 95%CI 1.17, 18.15). No subjects had positive CB-CAPs. T and B cell immunophenotypes and SARS-CoV-2 serologies did not differ by group. In heatmap analyses, higher autoantibody variety was seen among those with infection in the early pandemic. ConclusionIn this sample, having COVID-19 infection in the earlier (pre-2/1/2021) vs. later pandemic was associated with more CTD symptoms, ANA positivity, and autoantibody reactivities. Earlier SARS-CoV-2 variants circulating in a less vaccinated population with less natural immunity may have been more immunogenic.

Severe Intraocular Inflammation After Intravitreal Injection of Faricimab: A Single-Site Case Series of Six Patients

To describe the patient characteristics and clinical course of severe intraocular inflammation (IOI) following intravitreal injection (IVT) of faricimab. Retrospective case series. Case series at a single French academic center (Dijon University Hospital) where 263 patients were treated with faricimab IVT between January 9, 2024 and May 7, 2024. Over the 4-month period, a total of 1659 eyes (1338 patients) received anti-vascular endothelial growth factor (anti-VEGF) IVTs for a total of 3510 IVTs, of which 343 eyes (263 patients) received faricimab IVTs for a total of 971 IVTs. Overall, 6 pretreated eyes with neovascular age-related macular degeneration that were switched to faricimab developed severe unilateral IOI following faricimab IVT (1/162 injections [0.62%]), including 5 eyes presenting with a severe anterior and intermediate uveitis mimicking infectious endophthalmitis. All eyes were normotensive and presented with mild to moderate pain and predominantly moderate vitritis, associated with granulomatous keratic precipitates in 2 eyes and nonocclusive vasculitis in one eye. The clinical presentation, sterile vitreous sample culture, and rapid improvement with treatment made the diagnosis of infectious endophthalmitis unlikely. Four patients out of 6 did not recover their pre-IOI visual acuity, with an average visual loss of +0.2 logMAR. Two patients had positive antinuclear antibodies, including one with a history of cutaneous lupus. In this case series, we reported 6 cases of severe IOI after intravitreal faricimab over 4 months in a single French center with an estimated incidence rate of 0.6% per injection. Future real-world data will contribute to a better evaluation of the epidemiology of this rare inflammatory adverse event related to intravitreal faricimab.

Comparison of serum exosome miRNA from patients with Raynaud's phenomenon with positive and negative serum antinuclear antibodies.

To compare the microRNAs (miRNAs) contained within serum exosomes isolated from patients with Raynaud's phenomenon (RP) and negative antinuclear antibodies (ANA) to the miRNA contained in serum exosomes isolated from patients with RP and positive ANA. Serum exosomes were isolated employing a polymer precipitation procedure. Next Generation Sequencing (NGS) was used to identify the miRNAs contained in the exosomes isolated from the two clinical cohorts and to analyse the differences in their contents. The NGS results identified six miRNAs that displayed significant differences in their content between serum exosomes from patients with RP with negative serum ANA compared to miRNAs contained in serum exosomes from patients with ANA-positive RP. A comparative analysis of miRNAs contained within serum exosomes of patients with RP and negative ANA vs. samples from patients with RP and positive ANA identified several differentially expressed miRNAs that may represent non-invasive biomarkers to assist in the identification of patients with RP at risk of evolving into systemic sclerosis.

High antinuclear antibody titer is associated with increased mortality risk in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a diagnosis of exclusion, requiring that potential etiologies of interstitial lung disease be ruled out. Antinuclear antibody (ANA) testing is commonly performed in individuals with IPF, but the clinical significance of ANA positivity remains uncertain. A retrospective search identified 161 patients diagnosed with IPF between May 2010 and January 2021. Data on ANA titers at the time of diagnosis were available in all cases. Mean age of the patients was 66.4 ± 9.6 years; 70.8% were male. ANA titers were high (≥ 1:160) in 25.4% of the cohort. Baseline characteristics were comparable between those with high and low ANA titers. During follow-up (median 28 months), 93 patients (57%) died. On Cox proportional-hazards analysis with lung transplantation entered as a competing risk and adjusting for potential confounders (age, sex, and baseline forced vital capacity and diffusing lung capacity for carbon monoxide), ANA ≥ 1:160, as a dichotomized variable, was significantly associated with case-specific mortality (HR 2.25, 95% CI 1.14−4.42, P = 0.02) and older age (for each 10-year increment, HR 1.55, 95% CI 1.07−2.25, P = 0.02). High ANA titers appear to be associated with increased mortality in IPF. This finding emphasizes the potential prognostic value of ANA testing. Further studies are needed to validate these findings and explore their implications for patient management.

Clinical characteristics of pediatric noninfectious uveitis and risk factors for severe disease: a single-center study

ObjectivesWe aimed to present the demographic, clinical, laboratory, and treatment data of children with non-infectious uveitis and to evaluate the risk factors for the development of complications and the need for biological treatment.MethodPatients diagnosed with non-infectious uveitis in childhood and followed up for at least 1 year were included in the study. Demographic data, including age, gender, age at diagnosis, uveitis in first-degree relatives, and rheumatologic diseases, were obtained retrospectively from medical records. The presence of complications or the need for biologic therapy was considered a composite outcome suggesting severe disease.ResultsThe study included 123 patients (female: n = 59, 48%). The mean age at diagnosis was 14.89 ± 4.86 years. Uveitis was symptomatic in 104 patients (84.6%). Approximately one-quarter of the patients had at least one rheumatic disease (n = 35, 28.5%), the most common being juvenile idiopathic arthritis. Thirty-three patients (26.8%) had anti-nuclear antibody positivity. Biologic agents were needed in 60 patients (48.8%). Complications developed in 14 patients (11.4%). Early age at disease onset (aOR, 0.875; 95% C.I. 0.795–0.965, p = 0.007) and female gender (aOR, 2.99; 95% C.I. 1.439–6.248, p = 0.003) were significantly associated with the need for biologic treatment, while Behçet’s disease (BD) was strongly associated with uveitis-related complications (aOR, 14.133; 95% C.I. 2.765–72.231, p = 0.001).ConclusionWe suggest that among pediatric patients with non-infectious uveitis, females, those with an early age of disease onset, and those with BD need to be closely monitored due to a significantly increased risk of severe disease.Key Points• Limited data exist on the clinical course of non-infectious uveitis in children and the associated risk factors for severe disease.• Our study reveals that nearly a quarter of pediatric patients with non-infectious uveitis also have a rheumatic disease.• Among pediatric patients diagnosed with non-infectious uveitis, we observed an increased risk of severe disease in those with an earlier onset age, in female patients, and in those diagnosed with Behçet’s disease.

Immunological testing for female infertility: a modern view on the problem

Introduction. According to various estimates, in Russia 10 to 20 % of people of reproductive age are infertile. Changes in the immune system play a key role in the etiology and treatment of various infertility forms. The active introduction of immunological testing into clinical practice can potentially improve the results of infertility diagnostics and treatment.Aim: to analyze the current literature data on immunological testing in female infertility, as well as to assess its potential role in infertility diagnostics and treatment.Materials and Methods. There was conducted a search for publications in the electronic databases PubMed and eLibrary by using the following keywords and their combinations: "infertility", "immunology", "immune system", "immunological testing", "diagnostics", "treatment". The articles were evaluated in accordance with the PRISMA recommendations. Ultimately, 88 publications were included in the review.Results. Testing for antiphospholipid antibodies (APA) may be useful for women undergoing assisted reproductive technology (ART) therapy, as these antibodies increase the risk of pregnancy complications and thrombotic risks associated with ovarian stimulation, but studies assessing AFA effect on in vitro fertilization (IVF) outcomes have ambiguous results. The presence of antithyroid antibodies (ATA) may be associated with infertility, so their assessment is indeed important to determine treatment tactics. It has been suggested that antinuclear antibodies (ANA) may affect reproductive function by disrupting trophoblast cell development and interfering with RNA transcription, which may lead to lowered reproductive success. Studies have shown that patients with a positive ANA data have a lower incidence of pregnancy and a higher rate of miscarriages after IVF procedure. The human herpes virus type 6 (HHV-6) affects female fertility and is often the cause of spontaneous termination of pregnancy. B-cell lymphoma protein 6 (BCL-6) can serve as an important prognostic biomarker to identify individuals with endometriosis and related reproductive disorders, including idiopathic infertility. Evaluation of endometrial decidualization can be a useful tool to assess readiness for endometrial implantation and provide opportunities for targeted therapeutic interventions. The issue of testing for NK-cells in patients undergoing infertility screening remains controversial due to the difficulties of standardizing testing recommendations.Conclusion. To date, there is a limited number of reliable data on the role of various immunological tests in infertility diagnostics and treatment. With the exception of testing for AFA in patients with RPL, as well as for thyroid-stimulating hormone (TSH) and anti-thyroperoxidase antibodies (TPOAb) in patients undergoing therapy using various types of assisted reproductive technologies, the remaining immunological tests provide scant data to justify their routine use in clinical practice. The major limitations of existing studies are coupled to a small patient sample, as well as heterogeneity of inclusion criteria, patient groups and research methods.

Successful Steroid Therapy in a Child with Suspected Autoimmune Hepatitis

Introduction: Autoimmune Hepatitis (AIH) is an unexplained cause of chronic and progressive liver inflammation. The incidence of AIH is about 4.82/per 100,000 people in Korea, but based on global research the incidence is increasing and it should be taken more seriously. Laboratory and imaging tests were performed which led to the diagnosis of AIH but to diagnose AIH is difficult. Steroid therapy is an option for this patient by considering the side effects that are well-monitored. A favourable outcome was shown and this report is expected to highlight the importance of early diagnosis and treatment in AIH cases. Case presentation: A 6-year-old, 5-month-old girl presented to Dr. Soetomo General Academic Hospital, Surabaya with jaundice for 2 weeks. She had been unable to walk for the past 1 month due to pain in both legs, nausea and vomiting, anorexia, right-sided abdominal pain, and an enlarged abdomen. She has had a history of fever for the past 1 month. Laboratory parameters showed cholestasis, abnormal liver function test (aspartate aminotransferase (AST) 1406 U/L, alanine aminotransferase (ALT) 1392 U/L, and prolonged coagulation factor), and positive antinuclear antibody (ANA) test (79.10 AU/mL). Hepatitis markers were negative. Liver biopsy and autoantibodies examination (LKM and SMA) was not done due to limited facilities. Hepatitis, cholecystitis, and ascites were noted on abdominal ultrasonography. Ascites and cholecystitis were seen on an abdominal CT scan. Steroid therapy was administered and there was improvement in clinical condition and laboratory results following two weeks duration of treatment. Conclusion: This case report illustrates that steroid treatment for a child with AIH results in a good improvement and provides achievement of treatment goals following existing guidelines. The use of steroid therapy in suspected cases of AIH, without further diagnostic modalities, may be of value in the prevention of further liver damage, especially in healthcare settings with limited resources.

ANA Profile in Population of West Bengal

Antinuclear antibodies (ANA) are significant biomarkers that are used to detect and classify autoimmune connective tissue disorders more efficiently. This paper provides a thorough overview of all the ANA profiling procedures, their testing advancements, clinical significance, and future directions. This study aimed to analyze the ANA profiles along with the prevalence of specific antibodies in patients presumed to have been diagnosed with autoimmune disorders in an Eastern Indian tertiary care hospital. The results were correlated with demographic data to conclude. ANA profiles of 48 patients from Peerless Hospitex Hospital, Kolkata were evaluated between January 24 to June 15, 2024. Out of them, 13 patients (27%) had positive ANA profiles. The most prevalent autoantibodies detected were SS-A and SS-B, which occurred in 7 patients (53.85%), followed by PM-Scl in 4 patients (30.77%). The study demonstrates how the ANA profile varies among different age groups, with the highest prevalence of 6 patients (46.15%) seen in the 60–75 age range. The clinical symptoms of diseases like autoimmune hepatitis, polymyositis, dermatomyositis, PSS (progressive systemic sclerosis), SLE (Systemic Lupus Erythematosus), and Sjogren's syndrome align with the ANA profile findings. This study offers insights into the distribution of autoantibodies targeting antigens present in ANA profiles, using clinical samples collected from a 550-bed tertiary care hospital in Eastern India. The findings underscore the need for comprehensive diagnostic approaches to autoimmune disorders.

PTBP1 protects Y RNA from cleavage leading to its apoptosis-specific degradation

Some RNAs such as 28S rRNA, U1 small nuclear RNA (snRNA), and Y RNAs are known to be cleaved during apoptosis. The underlying mechanism, functions, and biological significance of RNA degradation in apoptosis remain elusive. Y RNAs are non-coding RNAs widely conserved from bacteria to mammals, and are major components of Ro ribonucleoprotein (RNP) complexes which contain the 60 kDa Ro protein (SS-A) and the 50 kDa La protein (SS-B). The autoantigenic Ro and La proteins were identified by autoantibodies present in the sera from patients with Systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SjS). We previously identified novel, functional small RNAs named AGO-taxis small RNAs (ASRs) that are specifically bound to Argonaute protein 1 (AGO1), which are processed from Y RNAs. Cell-free analysis combined with fractionation methods revealed that the apoptosis-specific biogenesis of ASRs or cleavage of Y RNA was induced by truncation of polypyrimidine tract-binding protein 1 (PTBP1), which is an endoribonuclease inhibitor of Y RNAs by caspase 3. Caspase 3-resistant PTBP1 mutant protected cleavage of Y RNAs in apoptosis induced by staurosporine. Furthermore, caspase 3-resistant PTBP1 mutant knock-in mice showed elevated cytokines, dysregulation of the germinal center formation compared to the wild-type mice at LPS stimulation, and high positivity of antinuclear antibody. Those results suggest that cleavage of Y RNAs or biogenesis of ASR during apoptosis has critical biological functions and their deregulation result in immune dysregulation and the formation of autoantibody, possibly leading to the development of autoimmune diseases.

O-201 Antinuclear antibodies in women with recurrent early pregnancy loss: prevalence and impact on subsequent pregnancy outcome

Abstract Study question What is the prevalence of antinuclear antibodies (ANAs) in women with recurrent early pregnancy loss (REPL) and do they affect subsequent pregnancy outcome? Summary answer The prevalence of ANAs in women with REPL was 13.0%, and their presence did not negatively impact subsequent pregnancy outcomes, including EPL and livebirth rates. What is known already An etiological factor cannot be identified in more than half of the couples experiencing REPL. Immunologic mechanisms could be involved, with the presence of autoimmune disease (AD) associated to lower reproductive outcomes. For the mere presence of ANAs, in the absence of AD, the evidence on the association with REPL is controversial, with most studies having a small sample size with important clinical and methodological heterogeneity. Study design, size, duration This is a single-centre, retrospective cohort study from a tertiary referral hospital including 960 women referred for REPL between January 2014 and December 2019. During the entire study period, maternal serum ANA detection was part of the routine diagnostic REPL work-up, defined as two or more pregnancy losses before the 10th week of gestation, including previous spontaneous conceptions and pregnancies following autologous IVF/ICSI treatment. Participants/materials, setting, methods Women under the age of 40 at ANA analysis were eligible for inclusion. Confirmed AD, uterine anomalies, parental chromosomal abnormalities and uncontrolled endocrine disorders were exclusion criteria. The prevalence of positive ANA titers and the impact of ANA positivity on the outcome of a subsequent pregnancy were investigated with EPL rate as the main outcome parameter and biochemical pregnancy rate, clinical miscarriage rate and live birth rate as secondary outcome measures. Main results and the role of chance Positive ANA screening at a titer of ≥ 1/80 was observed in 125/940 women (13.0%), a prevalence in line with previously published data in the general population not experiencing REPL. There were no statistically significant differences in maternal age, body mass index, ethnicity, or conception method between ANA-positive and -negative women. No higher number of previous EPLs was observed in ANA-positive compared to ANA-negative women (respectively 2.7 versus 2.8, p = 0.06). Women with ANAs had significantly more thyroid antibodies (21.6% versus 10.2%, p &amp;lt; 0.001). For a subsequent pregnancy, no association was observed between ANA positivity and reproductive outcome with an unadjusted EPL rate of 30/86 (34.9%, ANA-positive) versus 206/509 (40.5%, ANA-negative, p = 0.32). Logistic regression analysis did not identify ANAs as an independent predictive risk factor for additional EPL (OR 0.73, 95%CI 0.45-1.20, p = 0.22). Similarly, there was no significant difference in live birth rates between both groups (p = 0.5), with 54/86 (62.8%) in ANA-positive and 300/509 (58.9%) in ANA-negative patients. Limitations, reasons for caution The current data are limited by the absence of a formal control group without REPL, the retrospective nature of the study and potential bias due to unmeasured confounders. Wider implications of the findings These findings further questions systematic ANA measurement in the diagnostic work-up of REPL without AD. Furthermore, when ANAs are detected, patient counselling and treatment adaptations should be considered with caution, given our inability to eventually detect any significant differences in the pregnancy outcomes between ANA-positive and -negative REPL patients. Trial registration number not applicable

Association of focus score and extraglandular involvement in Sjögren's syndrome: A study on antinuclear antibodies and minor salivary gland pathology.

This study aimed to investigate the relationship between patients with and without extraglandular involvement in Sjögren's syndrome (SS) by analyzing ANA (antinuclear antibody) and ENA (extractable nuclear antigen) results and minor salivary gland pathology findings. A total of 265 (245 females; 20 males; mean age: 50.4±12.4; range, 19 to 79 years) patients diagnosed with SS were included in the retrospective cohort study between March 1, 2011, and December 1, 2021. Detailed documentation was performed, capturing demographic characteristics, clinical information, laboratory findings, medication usage, and manifestations of the syndrome. The patients were divided into two groups, with (78 females; 8 males; mean age: 52.7±11.5; range, 22 to 78 years or without (167 females; 12 males; mean age: 49.3±12.8; range, 19 to 79 years extraglandular involvement. The mean follow-up duration was 63.1±31.9 months. Extraganular involvement, including joint involvement, lung involvement, central nervous system involvement, hematological involvement, hepatitis, and lymphoma, was observed in 32.5% of the patients. Patients with extraglandular involvement required multiple medications, while those with only glandular involvement predominantly used hydroxychloroquine. The mean duration from SS diagnosis to extraglandular involvement was 15.2±27.8 months. The comparison between patients with and without extraglandular involvement revealed a significant association between higher focus scores (FS) and extraglandular manifestations. However, no significant differences were observed in terms of ANA positivity, ANA titers, or ENA positivity. Regression analysis indicated that age and FS were linked to systemic involvement. This study highlights the importance of FS as a predictive indicator for extraglandular manifestations in SS. Advanced age was found to be associated with an increased likelihood of extraglandular involvement. Assessing FS and age can aid in predicting extraglandular manifestations.

Antinuclear antibody staining patterns by indirect immunofluorescence assay observed in patients from a tertiary health center in Latin America

Introduction/ObjectiveThis study aimed to describe the frequency of antinuclear antibody (ANA) staining patterns by indirect immunofluorescence assay observed in patients from a tertiary health center in Latin America. Materials and methodsThis retrospective, descriptive, and observational study evaluated data from all patients undergoing antinuclear antibody indirect immunofluorescence assay from a single-tertiary center (University Hospital Fundación Valle del Lili, Cali-Colombia) in 2020. ResultsOne thousand and eight patients met the inclusion criteria. The median patient age was 47 (34–59.2) years, and most were female (769, 75.3%). A positive ANA immunofluorescence assay was observed in approximately two-thirds of patients (664, 65.8%). ANA test results were primarily used to exclude a suspected diagnosis in approximately half of the patients (466, 46.2%). Thirty-seven percent (250/664) of the cohort with ANA-positive titers had a systemic autoimmune rheumatic disease (SARD). The most prevalent SARDs included rheumatoid arthritis (RA) (55, 8.2%) followed by systemic lupus erythematosus (SLE) (37, 5.5%). The vast majority of ANA-positive patients had a reported speckled pattern (anti-cell [AC]-2,4,5; 269; 40.5%) followed by homogenous (AC-1; 266; 40%), nucleolar (AC-8,9,10; 46; 6.9%), and centromere (AC-3; 16; 2.4%). The most frequent patterns observed among SLE patients included homogenous (AC-1) patterns in 17 (45.9%) patients, speckled (AC-2,4,5) nuclear patterns in 11 (29.7%) patients, mixed patterns in 7 (18.9%) patients, and reticular/anti-mitochondrial antibody (AMA, AC-21) cytoplasmic patterns in 2 (5.4%) patients. ConclusionThis study is the first to describe ANA patterns in a Colombian population. Speckled and homogenous patterns were predominant in patients with SARDs.

Real-world experience of thrombopoietin receptor agonists in pediatric immune thrombocytopenia: a report from a Chinese tertiary children's hospital.

Primary immune thrombocytopenia (ITP) is the most common bleeding disorder in children. There are approximately 20% pediatric ITP patients respond poor to corticosteroids as first-line treatment. Recently thrombopoietin receptor agonists (TPO-RAs) have been used to treat refractory ITP and have achieved certain therapeutic effects. To investigate the efficacy and safety of TPO-RAs in the treatment of pediatric ITP, we conducted this real-world study. Fifty-three pediatric patients with ITP who did not respond well to corticosteroids were treated with TPO-RAs. Clinical data, including therapeutic response rate, changes in platelet (PLT) count, and adverse events (AEs) were collected. Of the 51 evaluable patients, 37 (72.5%) responded to TPO-RAs. Patients aged >4 years had a higher response rate than those aged ≤4 years (81.1% vs. 50.0%, P=0.04). There was no effect of sex, duration of disease, prior therapy, Mycoplasma pneumoniae (MP) immunoglobulin M (IgM) positivity, antinuclear antibody (ANA) positivity, CD4/CD8 ratio or baseline PLT count on the response rate (P>0.05). Other than 10 patients with PLT counts that exceeded the upper limit of normal, AEs were sporadic, including increased aminotransferase levels, cough, headache, and vomiting. TPO-RAs exhibited good clinical efficacy in pediatric ITP patients who failed to respond to first-line treatment, especially patients aged >4 years, and the side effects were minor.

Referrals for rheumatologic evaluation following a positive antinuclear antibody test result. A cross-sectional single center Brazilian study

BackgroundIn general, patients are referred for rheumatological evaluation due to isolated laboratory abnormalities, especially antinuclear antibody (ANA) positivity, with the risk of more severe patients remaining on the waiting list for longer than desired. The aim of this study was to analyze the demographic, clinical, and laboratory information of patients referred to a specialized rheumatological care unit because of positive antinuclear antibody.MethodsThis is a retrospective study of 99 out of 1670 patients seen by the same rheumatologist between 01/01/2011 and 01/01/2019. Patients whose referrals were exclusively due to the ANA test result and the specialist’s final diagnosis being “abnormal finding of serum immunological test” (ICD-10 R769) were included. Sociodemographic, clinical, and laboratory information were extracted from the consulting rheumatologist’s chart. Descriptive statistics were used for data analysis.ResultsA total of 99 patients were included, most of whom were female (84.8%) with a median age of 49 years. At the moment of specialist’s appointment, 97 patients (97.9%) repeated the ANA test, and 77 patients remained positive. Of these, only 35 (35.35%) were in a high titer range (greater than or equal to 1:320). Complete blood count for cytopenia’s investigation was not performed in a high percentage of patients (22.2%), as well as urinalysis (31.3%). In addition, more than 70% of patients score 0 to 1 classification criteria for Systemic Lupus Erythematosus, according to SLE - ACR 1987 (American College of Rheumatology) and SLICC 2012 (Systemic Lupus International Collaborating Clinics).ConclusionsMost patients are still referred for specialized evaluation due to the misinterpretation of laboratory tests that were inappropriately requested in patients without clinical evidence of autoimmune rheumatic disease.