Positive Antinuclear Antibody Titer Research Articles

A Case Report of Mixed Connective Tissue Disease Predominantly Manifesting as Systemic Sclerosis in a Middle-Aged Nepali Woman

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder, first described in 1972, that presents with overlapping features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis of MCTD is complex and often delayed due to its varied clinical manifestations and the requirement of serological confirmation, particularly the presence of anti-U1 RNP antibodies. Despite its global prevalence, data on MCTD are limited, especially in the South Asian population.  Case Report: We present the case of a 42-year-old Nepali woman with a decade-long history of myalgia, muscle weakness, and joint pain, initially misdiagnosed as rheumatoid arthritis. Over time, she developed Raynaud phenomenon, dysphagia, and progressive muscle weakness, which prompted further investigation. Serological testing revealed elevated levels of anti-U1 RNP antibodies and a positive antinuclear antibody (ANA) titer, confirming the diagnosis of MCTD according to the Alarcón-Segovia criteria. The patient was successfully managed with a regimen of corticosteroids, hydroxychloroquine, and nifedipine, resulting in significant symptomatic improvement.  Discussion: This case underscores the diagnostic challenges associated with MCTD, a condition that may present with nonspecific symptoms and mimic other rheumatic diseases. The prolonged diagnostic journey of this patient highlights the need for heightened clinical suspicion and comprehensive serological testing in patients with overlapping connective tissue disease features. Furthermore, the case contributes to the limited body of literature on MCTD in the South Asian population, emphasizing the importance of early recognition and tailored management strategies to improve patient outcomes.  Conclusion: MCTD is a complex and under-recognized autoimmune disorder, particularly in the South Asian context. This case report highlights the importance of considering MCTD in the differential diagnosis of patients with multi-systemic involvement and underscores the role of serological testing in confirming the diagnosis. Early diagnosis and appropriate management are crucial in mitigating disease progression and improving the quality of life for patients with MCTD.

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 < 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

A case of systemic lupus erythematosus in a patient with Noonan syndrome with recurrent severe hypoglycaemia.

Noonan syndrome (NS) is a dominantly inherited genetic disorder with mutations in genes encoding components or regulators of the Rat sarcoma virus/mitogen-activated protein kinase pathway. Its diagnosis is based on characteristic features, including typical facial features, a short stature, congenital heart disease, mild developmental delay, and cryptorchidism. Patients with NS sometimes develop autoimmune diseases, such as Hashimoto's thyroiditis and, rarely, systemic lupus erythematosus (SLE). We herein present a 29-year-old Japanese female with NS complicated by SLE and repeated severe hypoglycaemia. The patient was diagnosed with SLE based on thrombocytopenia, nephritis, a positive antinuclear antibody titre (1:640), and a positive anti-dsDNA antibody. The patient was treated with a glucocorticoid, mycophenolate mofetil, and tacrolimus, which attenuated both SLE and hypoglycaemia. Since insulin receptor antibody levels were higher to the upper normal range and decreased after treatment, hypoglycaemia probably appeared to be attributed to type B insulin resistance syndrome. We herein present the first case of SLE in NS complicated by type B insulin resistance syndrome. Although NS is a rare disease, we need to consider the complication of autoimmune diseases, including SLE.

Machine learning approaches to identify systemic lupus erythematosus in anti-nuclear antibody-positive patients using genomic data and electronic health records

BackgroundAlthough the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) has required at least a positive anti-nuclear antibody (ANA) titer (≥ 1:80), it remains challenging for clinicians to identify patients with SLE. This study aimed to develop a machine learning (ML) approach to assist in the detection of SLE patients using genomic data and electronic health records.MethodsParticipants with a positive ANA (≥ 1:80) were enrolled from the Taiwan Precision Medicine Initiative cohort. The Taiwan Biobank version 2 array was used to detect single nucleotide polymorphism (SNP) data. Six ML models, Logistic Regression, Random Forest (RF), Support Vector Machine, Light Gradient Boosting Machine, Gradient Tree Boosting, and Extreme Gradient Boosting (XGB), were used to identify SLE patients. The importance of the clinical and genetic features was determined by Shapley Additive Explanation (SHAP) values. A logistic regression model was applied to identify genetic variations associated with SLE in the subset of patients with an ANA equal to or exceeding 1:640.ResultsA total of 946 SLE and 1,892 non-SLE controls were included in this analysis. Among the six ML models, RF and XGB demonstrated superior performance in the differentiation of SLE from non-SLE. The leading features in the SHAP diagram were anti-double strand DNA antibodies, ANA titers, AC4 ANA pattern, polygenic risk scores, complement levels, and SNPs. Additionally, in the subgroup with a high ANA titer (≥ 1:640), six SNPs positively associated with SLE and five SNPs negatively correlated with SLE were discovered.ConclusionsML approaches offer the potential to assist in diagnosing SLE and uncovering novel SNPs in a group of patients with autoimmunity.

Diagnosis of systemic lupus erythematosus in a dog with an atypical presentation of pleuritis

AbstractA 3‐year‐old labradoodle presented with prior history of generalised seizures and had recently developed acute pyrexia and shifting leg lameness, with joint effusions in several joints. The dog also later developed pleuritis with an exudative pleural effusion. Cytological findings for all joint effusions were consistent with immune‐mediated polyarthritis. Suspected lupus erythematosus cells were seen in the joints and pleural fluid, which were confirmed with Feulgen staining. Together with a positive antinuclear antibody titre, the dog was diagnosed with systemic lupus erythematosus, which responded to immunosuppressive doses of prednisolone. This case report describes the insidious nature of systemic lupus erythematosus, a rare disease that can imitate many different conditions. It is also the first reported case of lupus erythematosus cells in pleural effusion in veterinary medicine, highlighting the importance of lupus erythematosus cells as a valuable diagnostic aid to further support the diagnosis of systemic lupus erythematosus and enable early treatment to be initiated.

Coronary Artery Ectasia as an Autoimmune Disease Paradigm in a Cross-Sectional Case-Control Study

Coronary artery ectasia (CAE) is defined as local or generalized aneurysmal dilatation of the coronary arteries. CAE likely represents an exaggerated form of excessive vascular wall remodeling in different clinical settings such as atherosclerosis, vasculitides, connective tissue disorders, hereditary collagen defects, bacterial infections, and congenital malformations. In the present case-control study, we investigated whether the incidental finding of CAE in patients who undergo coronary angiography is associated with presence of autoimmune reactivity. From 2019 to 2022, we identified all consecutive patients with CAE (n=319) on elective or emergency coronary angiography (n=7,458). We furthermore included 90 patients with nonectatic coronary arteries as a control group. Antinuclear antibody (ANA) titer was measured in both groups using the indirect immunofluorescence method from peripheral blood samples. The prevalence of CAE in our study cohort was 4.3%. Among patients with CAE (n=319), presence of positive Antinuclear antibody (ANA) titer was identified in 128 patients (40%). Only 18 patients (20%) from the control group had positive ANA titer. There was a statistically significant greater percentage of patients with positive ANA titer among patients with CAE than among controls (chi-square=12.39; p <0.001), with an odds ratio of 2.68. Among patients with CAE, there is an increased prevalence of positive ANA titer, suggesting an underlying autoimmune disease. Screening for autoimmune reactivity could be a reasonable diagnostic strategy in patients who undergo coronary angiography with an incidental finding of coronary ectasia because the number needed to screen for positive ANA titer in this subgroup of patients is only 5.

Significane of determining antinuclear antibodies in systemic connective tissue disorders in children

Systemic connective tissue diseases (SCTD) are characterized by systemic autoimmune inflammation and are accompanied by development of antinuclear antibodies (ANA). Our aim was a comparative analysis of ANA in blood serum in children with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The study included 50 patients with SLE, 50 patients with RA who were treated at the National Medical Research Center of Childrens Health. Median age was 12,2 y. o. (9-15.5). The titers of ANA and the cell fluorescence type were determined with the indirect immunofluorescence reaction (IFR) using the HEp-2 cell line (Immco Diagnostics, Inc, USA), as well as the concentration of antibodies to double-stranded DNA (adsDNA) in blood serum samples of the children detected by immunochemiluminescence (ICM) woth Elia dsDNA (Thermo Fisher Scientific, USA). A positive ANA titer and adsDNA were found, respectively, in 98% and in 48% in children with SLE. A positive ANA titer and adsDNA was detected in 100% and in 4% of children with RA, respectively. Highly positive ANA titers ( 1/1280) have been detected in 68% of children with SLE, and in 30% of children with RA. None of the RA patients with highly positive ANA titers had adsDNA. But, in patients with SLE, highly positive ANA titers and a positive dsDNA level were simultaneously detected in 16% of cases. There are both single types of cell fluorescence and their combinations in children with SLE and RA. Nuclear dot-like fluorescence was more common in children with SLE, cytoplasmic type, in children with RA, nucleolar type of glow was found only in children with RA. The revealed combinations of ANA and adsDNA titers in children with SLE and RA confirm the need for simultaneous use of RNIF and ICM.

Iatrogenic ANA: An emerging source of expensive diagnostic confusion.

Intravenous immune globulin (IVIg) therapy has been shown to be useful in a multitude of disorders. IVIg is produced from pooled human plasma; therefore, autoantibodies found in the general population are also present in IVIg and transferred to those being transfused. This can prove a particular hazard for screening and diagnostic tests based on autoantibodies. We present a patient who was found to have a positive antinuclear antibody (ANA) titer after multiple IVIg transfusions, resulting in diagnostic confusion and unnecessary workup. A 45-year-old gentleman was diagnosed with atypical CIDP, initiated on a course of IVIg, and sent for inpatient rehabilitation. However, recovery was complicated by multiple readmissions for recurrent weakness, and as part of the workup for other etiologies, an ANA was found to be positive. Sub-serologies and paraneoplastic autoantibody panel were negative. In the absence of clinical symptoms, we recommended continued monitoring and repeat ANA testing 6months after the last dose of IVIg; as any drug needs 5 half-lives to be eliminated from the body. Clinicians should consider any recent IVIg treatments when evaluating the pre-test probability of detecting an underlying connective tissue disease with ANA screening. Indiscriminate ANA levels in patients recently given IVIg lead to unnecessary and expensive further testing and consultation.

A Nordic screening guideline for juvenile idiopathic arthritis-related uveitis.

The purpose of this perspective was to shed light on screening of uveitis among Nordic children with juvenile idiopathic arthritis (JIA). A literature search was conducted to review predictors of JIA-uveitis and previous JIA-uveitis screening recommendations. Predictors of uveitis in JIA are younger age and positive antinuclear antibody titre at onset of JIA, specific subtypes of JIA (extended and persistent oligoarthritis, rheumatoid factor negative polyarthritis and psoriatic arthritis) and short duration of JIA. Methotrexate and monoclonal tumour necrosis factor (TNF) inhibitor treatment reduce the risk JIA-uveitis. Children with all of the above risk factors should be screened frequently but if they receive TNF inhibitor or methotrexate therapy, they may be screened less frequently. Children with none of the risk factors do not benefit from long-term screening for uveitis. A guideline for intervals and overall length of screening was prepared considering currently known risk factors for JIA-uveitis, the Nordic population and previous guidelines.

ANSWERS LIE IN THE COMPLETE BLOOD COUNT: A CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS PRESENTING WITH ACUTE ST-WAVE ELEVATION MYOCARDIAL INFARCTION

ANSWERS LIE IN THE COMPLETE BLOOD COUNT: A CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS PRESENTING WITH ACUTE ST-WAVE ELEVATION MYOCARDIAL INFARCTION

Immunologic phenotype of patients with long-COVID syndrome of 1-year duration.

BackgroundThe pathophysiology of long-COVID remains unknown, and information is particularly limited for symptoms of very long duration. We aimed to assess the serological, T-cell immune responses and ANA titers of patients with long-COVID-19 syndrome of 1-year duration.MethodsProspective, longitudinal study of hospitalized COVID-19 patients followed-up for 12 months. Sequential blood samples and COVID-19 symptom questionnaires (CSQ) were obtained, and humoral and cellular immune responses, antinuclear antibodies (ANA) and inflammation biomarkers were analyzed.ResultsOf 154 patients discharged from hospital, 72 non-vaccinated with available CSQ in all visits were included. Of them, 14 (19.4%) reported persistent symptoms both at 6-months and 12-months, mainly asthenia (15.3%), myalgia (13.9%), and difficulty concentrating/memory loss (13.9%). Symptomatic patients were more frequently women, smokers, showed higher WHO severity score, and a trend to higher ICU admission. In the adjusted analysis, long-COVID syndrome was associated with lower frequency of detectable neutralizing antibodies (adjusted hazard ratio [aHR] 0.98; 95% confidence interval [CI], 0.97-0.99) and lower SARS-CoV-2-S1/S2 titers (aHR [95%CI] 0.14 [0.03–0.65]). T-cell immune response measured with a SARS-CoV-2-interferon-γ release assay was not different between groups. There was a higher frequency of positive ANA titers (≥160) in symptomatic patients (57.1% vs 29.3%, p=0.04), that was attenuated after adjustment aHR [95% CI] 3.37 [0.84-13.57], p=0.087. Levels of C-reactive protein and D-dimer were higher during follow-up in symptomatic patients, but with no differences at 12 months.ConclusionPatients with 1-year duration long-COVID-19 syndrome exhibit a distinct immunologic phenotype that includes a poorer SARS-CoV-2 antibody response, low-degree chronic inflammation that tends to mitigate, and autoimmunity.

Cluster phenotypes in a non-idiopathic pulmonary fibrosis fibrotic interstitial lung diseases cohort in Singapore.

BackgroundNon-idiopathic pulmonary fibrosis fibrosing interstitial lung diseases (F-ILDs) may demonstrate a progressive disease trajectory similar to idiopathic pulmonary fibrosis (IPF). We aimed to identify novel F-ILD phenotypes in a multi-ethnic South-East Asian population.MethodsF-ILD subjects (n=201) were analysed using unsupervised hierarchical cluster analysis and their outcomes compared against IPF (n=86).ResultsFour clusters were identified. Cluster 1 (n=53, 26.4%) comprised older Chinese males with high body mass index (BMI) and comorbidity burden, higher baseline forced vital capacity (FVC) percentage predicted and lower diffusing capacity of the lung for carbon monoxide (DLCO) percentage predicted. They had similar mortality to IPF. Cluster 2 (n=67, 33.3%) had younger female non-smokers with low comorbidity burden, groundglass changes on high-resolution chest computed tomography (HRCT) and a positive anti-nuclear antibody (ANA) titre ≥1:160. They had lower baseline FVC and higher DLCO, low mortality and slower lung function decline. Cluster 3 (n=42, 20.9%) consisted male smokers with low comorbidity burden, emphysema on HRCT and high baseline lung function. They had low mortality and slow lung function decline. Cluster 4 (n=39, 19.4%) was the highest risk and comprised of mainly Indians with high BMI. They had the highest proportion of ischemic heart disease (IHD) and previous pulmonary tuberculosis. Subjects had the lowest baseline lung function, highest mortality, and fastest lung function decline. Survival differences across clusters remained significant following adjustment for treatment.ConclusionsWe identified four distinct F-ILD clinical phenotypes with varying disease trajectories. This demonstrates heterogeneity in F-ILD and the need for complementary approaches for classification and prognostication beyond ATS/ERS guideline diagnosis.

Prevalence of antinuclear antibodies and rheumatoid factor titers in dogs with arthritis secondary to leishmaniosis (Leishmania infantum).

Dogs with infectious arthritis may occasionally exhibit positive serum antinuclear antibody (ANA) and rheumatoid factor (RF) titers; however, relevant data are sparse for arthritis secondary to canine leishmaniosis (CanL) caused by Leishmania infantum. We determined the prevalence of positive serum ANA and RF titers in dogs with arthritis secondary to CanL. Blood samples from adult, client-owned dogs with purulent arthritis secondary to CanL, without any comorbidities, were collected for diagnostic purposes. Serum ANA titers were measured by immunoperoxidase test and RF titers by the Rose-Waaler latex test. Twelve of 23 dogs enrolled prospectively in our study had clinical arthritis, and 11 of 23 had subclinical arthritis. Based on LeishVet clinical staging, 7 dogs had clinical stage II disease, 11 had clinical stage III disease, and 5 had stage IV. None of the 23 dogs was seropositive for ANA; 3 of 23 were positive for RF. ANA and/or RF seropositivity, in dogs with CanL-associated arthritis, appears to be weak, if present at all. Based on our results, positive serum ANA and RF titers should not be expected in dogs with arthritis secondary to CanL.

P239 Are patients with acute pericardial syndromes adequately screened for connective tissue diseases? Results from a single-centre study and comparison to European Society of Cardiology Guidelines

Abstract Background/Aims Pericardial syndromes (PS) comprising pericarditis, pericardial effusions, cardiac tamponade, and constrictive pericarditis, can be presenting features of connective tissue disease (CTD) including lupus (SLE) and rheumatoid arthritis (RA). PS comprise 0.1% of all hospital admissions and 5% of acute non-cardiac chest pain. PS occur as single episodes but recur in 30% of patients within 18 months after the first episode. The 2015 European Society of Cardiology (ESC) pericardial disease guidelines recommend assessment of NSAID response with follow-up and tests in those who are NSAID non-responders or who have recurrent PS. We audited the management of patients presenting with PS in a tertiary referral centre, using the 2015 ESC guideline standards to determine if investigations to uncover autoimmune diseases as a cause of PS were performed. Methods We obtained data on all patients coded with PS presenting to St George’s Hospital Emergency Department between Jan 1st, 2019, and October 31st, 2020. We also searched data including patients’ length of stay, test results including blood tests, imaging (X-ray, ultrasound, CT and MRI), initial management, outpatient follow-up, recurrence numbers and identifiable cause. Data were compared to the 2015 ESC guidelines. Results We identified 132 PS cases, of which 37 (28%) had recurrent pericardial disease. Of these, 15 (41%) were screened for connective tissue disease with antinuclear antibody (ANA) testing. Of those tested, nine (60%) had a positive ANA (titre 1/80 or greater), with three (33%) positive for extractable nuclear antigens (anti-Ro, anti-Sm and anti-RNP). Only 14 patients (38%) with recurrent disease had rheumatoid factor (RhF) tested, with four of these (29%) positive, while one of eight (12.5%) patients tested was anti-CCP antibody positive. Only 13 of 37 recurrent cases (35%) had both ANA and RhF tested. Furthermore, 37 of all PS cases (28%) were not followed up after initial presentation, while only five (14%) of recurrent cases received any follow up. By contrast, presumed infection tested serologically was found in only 7.8% of all cases tested, most commonly Mycoplasma or raised ASOT. Conclusion A high proportion of recurrent PS patients screened in our study had a positive ANA, ENA or RhF suggesting screening can identify new potential CTD, including SLE or RA. These patients require different treatment strategies to infectious PS. We demonstrated screening was inconsistent despite the absence of obvious infective causes in most cases and limited to 41% of patients with recurrent disease, which present the highest risk of association with CTD. ESC guidelines recommend all patients be followed up after 1 week, yet few high-risk patients received any outpatient review, from any speciality. There is a pressing need to ensure potential cases of CTD presenting as PS are not missed as doing so may prolong symptoms and worsen outcome. Disclosure D. Srikantharajah: None. V. Joseph: None. A. Kaul: None.

Evaluation of autoantibodies as predictors of treatment response and immune-related adverse events during the treatment with immune checkpoint inhibitors: Aprospective longitudinal pan-cancer study.

BackgroundThe presence of autoantibodies in the serum of cancer patients has been associated with immune‐checkpoint inhibitor (ICI) therapy response and immune‐related adverse events (irAEs). A prospective evaluation of different autoantibodies in different cancer entities is missing.Materials and MethodsIn this prospective cohort study, we included a pan‐cancer cohort of patients undergoing ICI treatment and measured a comprehensive panel of autoantibodies at treatment start and at the time point of first response evaluation. The presence and induction of autoantibodies (ANA, ENA, myositis, hepatopathy, rheumatoid arthritis) in different cancer entities were assessed and the association between autoantibodies and disease control rate (DCR), objective response rate (ORR), and progression‐free survival (PFS), as well as the development of grade 3 or higher irAEs were evaluated by logistic regression models, cox proportional hazard models, and Kaplan–Meier estimators.ResultsOf 44 patients with various cancer entities, neither the presence of any positive autoantibody measurement nor the presence of positive antinuclear antibodies (ANA) [≥1:80] at baseline was associated with the examined clinical endpoints (DCR, ORR, PFS) in univariable and multivariable analyses. After 8–12 weeks of ICI treatment, DCR, ORR, and PFS did not significantly differ between patients with and without any positive autoantibody measurement or positive ANA titers. The frequency of irAEs did not differ depending on autoantibody status of the patients.ConclusionAutoantibodies at treatment initiation or induction after 8–12 weeks of ICI treatment are not associated with treatment efficacy as indicated by DCR, ORR, and PFS or higher grade irAEs.

Clinical utility of anti-DFS70 for identifying antinuclear antibody-positive patients without systemic autoimmune rheumatic disease

The antinuclear antibody (ANA) test is a screening test for systemic autoimmune rheumatic disease (SARD). We hypothesised that the presence of anti-DFS70 in ANA-positive samples was associated with a false-positive ANA test and negatively associated with SARD. A retrospective analysis of patient samples received for ANA testing from 1 January 2016 to 30 June 2016 was performed. Patient samples underwent ANA testing via indirect immunofluorescence method and anti-DFS70 testing using enzyme-linked immunosorbent assay. Among a total of 645 ANA-positive samples, the majority (41.7%) were positive at a titre of 1:80. The commonest nuclear staining pattern (65.5%) was speckled. Only 9.5% of ANA-positive patients were diagnosed with SARD. Anti-DFS70 was found to be present in 10.0% of ANA-positive patients. The majority (51/59, 86.4%) of patients did not have SARD. Seven patients had positive ANA titre > 1:640, the presence of anti-double stranded DNA and/or anti-Ro60. The presence of anti-DFS70 in ANA-positive patients was not associated with the absence of SARD (Fisher's exact test, p = 0.245). The presence of anti-DFS70 was associated with a false-positive ANA test in 8.6% of our patients. Anti-DFS70 was not associated with the absence of SARD.

Study of the D-dimer, C-reactive protein, and autoantibodies markers among HBV infected patients in Babylon province, Iraq.

BackgroundHepatitis B can be defined as one of the dangerous diseases caused by the hepatitis B virus (HBV), which infects the liver and causes liver failure, cirrhosis, and death.AimsThis study aimed to evaluate the D-dimer, C-reactive protein (CRP), and autoantibodies markers among HBV-infected patients in Babylon province, Iraq, compared to a healthy control group.MethodsIn this cross-sectional study, all patients referred to GIT and liver centers in Merjan Medical City, Babylon, Iraq from January 2016 to January 2018 were screened for HBV infection by quantitative real-time polymerase chain reaction (qPCR). Antinuclear antibody (ANA), dsDNA, D-dimer, and CRP markers were examined using fluorescence technique in randomly selected patients and some healthy individuals as control group. Statistical analysis was performed using SPSS program.ResultsIn this study, 424 HBV patients from different areas of Babylon province, Iraq were enrolled. A total of 40 patients and 15 healthy participants were selected for evaluation of D-dimer, CRP, ANA, and dsDNA levels. The results of the distribution of HBV-infected patient by gender per area revealed that males accounted for a higher percentage than females in all parts of Babylon provinces. Also, a highly significant increase in serum levels was observed in the patients compared to the control subjects for all the studied parameters D-dimer, ANA, dsDNA, and CRP. Overall, 5.5% of HBV patients (3/40) had a positive ANA titer. None of the HBV patients had a positive dsDNA titer.ConclusionThis study showed that, HBV-infected patients had elevated levels of D-dimer and CRP compared to the control group. Also, the seropositivity titers of ANA and anti-dsDNA autoantibodies were low in Iraqi HBV patients.

75-Year-Old Man With Fever and Malaise

A 75-year-old Caucasian man presented to the emergency department following an episode of unresponsiveness and urinary incontinence. Recent history revealed fever, fatigue, generalized weakness, increased urinary frequency, anorexia, and a 10-lb unintentional weight loss over several months. His medical history was significant for previous exposure to asbestos with pleural calcification; recent painless truncal and upper extremity rash with biopsy, demonstrating weak granular deposition of complement C3 (indeterminate for early connective tissue disease manifestation or normal variant); positive antinuclear antibody (ANA) titer of unknown clinical significance; esophageal stricture treated with dilation; type 2 diabetes mellitus treated with metformin; hypertension treated with amlodipine and enalapril; and hyperlipidemia treated with atorvastatin.

A young girl with chronic isolated cervical lymphadenopathy found to have lupus lymphadenopathy, progressing to develop lupus nephritis: a case report

BackgroundSystemic lupus erythematosus is a rare autoimmune disorder, with the prevalence in Asia ranging from 30 to 50/100,000. The diagnosis of systemic lupus erythematosus is made according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria, and it does not contain lymphadenopathy as diagnostic criteria. However, lupus lymphadenopathy has an estimated prevalence of 5–7% at the onset of disease, and 12–15% at any stage of the disease.Case presentationA 19-year-old Sinhalese girl had neck nodules since the age of 5 years, which increased in size and became tender since 1 year. She had alopecia and joint stiffness for 6 months. She presented with a 5-day history of worsening joint pain, fever, and painful, enlarging cervical nodules. She had tender cervical lymphadenopathy, and a vasculitic rash on both lower limbs. She had pancytopenia, an erythrocyte sedimentation rate of 92, positive antinuclear antibody titer, and high anti-double-stranded deoxyribonucleic acid (DNA), with low C3 and C4 complements. She had a high reticulocyte count of 5%, with direct and indirect antiglobulin tests being positive, indicating autoimmune hemolytic anemia. Lymph node biopsy showed moderate reactive follicular hyperplasia, with scattered plasma cells and immunoblasts, with varying degree of coagulative necrosis, suggestive of lupus lymphadenopathy. On immunohistochemistry of the lymph node biopsy, Bcl2 was negative, excluding lymphoma. Contrast-enhanced computed tomography of abdomen and chest was normal with no hepatosplenomegaly or lymphadenopathy. Skin biopsy showed leukocytoclastic vasculitis. Later, with development of generalized edema, she was found to have impaired renal function, and renal biopsy showed lupus nephritis. She was started on hydroxychloroquine, prednisolone, and mycophenolate mofetil, and her symptoms improved and lymphadenopathy regressed.ConclusionIn the case of cervical lymphadenopathy in a patient with systemic lupus erythematosus, the possibilities of lupus lymphadenopathy, Kikuchi–Fujimoto disease, and lymphoma should all be considered, after excluding secondary infection due to immunosuppression. Histology confirms the differentiation of these pathologies. It is important to differentiate the cause for lymphadenopathy in systemic lupus erythematosus as the outcome and treatment varies. Lupus lymphadenopathy is usually generalized, but isolated cervical lymphadenopathy could also rarely be the first presentation of systemic lupus erythematosus. Lupus lymphadenopathy can be the only presenting feature, and needs a high index in suspecting systemic lupus erythematosus, though it is not included in the diagnostic criteria.

Efficacy and Feasibility of Programmed Death-1/Programmed Death Ligand-1 Blockade Therapy in Non-Small Cell Lung Cancer Patients With High Antinuclear Antibody Titers.

BackgroundImmune checkpoint inhibitor (ICI) therapy has been described to markedly improve patient survival. However, reports describing the antitumor therapeutic efficacy and safety of ICIs in patients with autoantibodies are scarce.MethodsThis study examined the efficacy and feasibility of ICIs in antinuclear antibody (ANA)-positive patients with non-small cell lung cancer (NSCLC). An ANA titer greater than 1:40 and 1:80 was defined as positive and high, respectively. Patients who were treated with ICIs at Saitama Medical University, International Medical Center between January 2016 and December 2018 were retrospectively reviewed.ResultsOne hundred and nineteen of the 266 patients (44.7%) who received nivolumab, pembrolizumab, and atezolizumab had positive ANA titers. Their median age was 69 (range, 39–84) years. The overall response rate of the ANA-positive patients was 35.9% (37/103), which was not less than that of the ANA-negative group. The median progression-free survival in the ANA-positive group was 6.3 months versus 4.3 months in the ANA-negative group (p = 0.08). Twenty-seven ANA-positive patients (10.2%) had high ANA titers. However, ICI efficacy was not decreased in these patients. Regardless of the cutoff of ANA titers (1:40 or 1:80), the rate of patients who experienced adverse events were not significantly different between the two groups.ConclusionThe administration of ICIs to ANA-positive patients has clinical benefits. The prevalence of adverse events in the ANA-positive group was not higher than that in the ANA-negative group.