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Contents of antinuclear antibodies (ANA), rheumatoid factor (RF), tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were measured in serum from 20 dogs with immune-mediated fever. Seven out of 20 patients were ANA positive, 1 out of 20 was positive to antibodies against extractable nuclear antigens (ENA), 1 out of 20 was positive to antibodies against deoxynucleoproteins (DNP), 2 out of 13 were RF positive and none out of 20 patients had antibodies against native DNA in the serum. TNF-α was not detected in any serum of 15 dogs with immune-mediated fever, while 10 out of 13 presented with elevated IL-6. The results varied between patients, but the IL-6 level was high in most of them. This indicate a role for IL-6 in the pathogenesis of immune-mediated fever in most cases. [ABSTRACT FROM AUTHOR]

Background: Systemic sclerosis (SSc) is considered by many to be one of the most severe autoimmune rheumatic diseases with lower prevalence observed in Northern Europe. No previous studies on the prevalence of SSc in Latvia have been conducted and the aim was to study the demographic and clinical data of patients with SSc in northeastern Europe country. Methods: This study was conducted in two main Latvian hospitals for adults and includes patients with SSc who were consulted between 2016 and 2021. Results: During the study period, 159 patients with SSc were consulted. The point prevalence on 1 January 2021 was 84.0 per million. Female to male ratio was 4.67:1, and highest gender ratio was observed in the age group 70–79-year (6.75:1). Antinuclear antibodies were present in 82.58% of patients, without gender difference. Centromere pattern was more frequently observed in females (40.19% vs. 19.04%), in contrast to speckled pattern (50.98% vs. 57.14%). At disease onset females tended to be younger (46.51 ± 13.52) than males (50.5 ± 16.64). Males had more diffuse cutaneous subtype, interstitial lung disease, pulmonary hypertension and esophageal dysmotility. More than half of patients received treatment with glucocorticoids at any point of the disease (68.31%), without gender difference. Conclusions: Systemic sclerosis is less common in Latvia than in other countries and regions. Due to its location, the data from Latvia are consistent with a north-south gradient in Europe. Gender ratio differences persisted in older age groups as well. Antinuclear antibodies presence did not differ between genders, but in female's centromere pattern was much more likely to be present. Males had more severe disease course, but in both genders more than half of patients received treatment with GCs at any point of the disease. [ABSTRACT FROM AUTHOR]

Objectives: 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. Patients and methods: A total of 265 (245 females; 20 males; mean age: 50.4±12.4 years; 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Abstract This study investigates the presence of antinuclear antibodies (ANA) in three primary synucleinopathies – Parkinson’s disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), compared to healthy controls. Autoinflammatory disorders typically involve the immune system mistakenly attacking the body’s own cells and start producing ANA. There is an increasing body of evidence that immune-mediated inflammation is a pathological feature linked to synucleinopathies. To investigate whether this could be autoimmune mediated we analyzed for ANA in the plasma of 25 MSA, 25 PD, and 17 DLB patients, along with 25 healthy controls, using the ANA HEp-2 indirect immunofluorescence antibody assay (ANA HEp-2 IFA). Contrary to initial expectations, results showed ANA HEp-2 positivity in 12% of PD, 8% of MSA patients, 18% of DLB patients, and 17% of healthy controls, indicating no increased prevalence of ANA in synucleinopathies compared to age-matched healthy individuals. Various ANA HEp-2 patterns were identified, but no specific pattern was associated with individual synucleinopathies. We conclude hereby that synucleinopathies are not associated with detectable presence of ANA in plasma.

This study investigates the presence of antinuclear antibodies (ANA) in three primary synucleinopathies – Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), compared to healthy controls. Autoinflammatory disorders typically involve the immune system mistakenly attacking the body's own cells and start producing ANA. There is an increasing body of evidence that immune-mediated inflammation is a pathological feature linked to synucleinopathies. To investigate whether this could be autoimmune mediated we analyzed for ANA in the plasma of 25 MSA, 25 PD, and 17 DLB patients, along with 25 healthy controls, using the ANA HEp-2 indirect immunofluorescence antibody assay (ANA HEp-2 IFA). Contrary to initial expectations, results showed ANA HEp-2 positivity in 12% of PD, 8% of MSA patients, 18% of DLB patients, and 17% of healthy controls, indicating no increased prevalence of ANA in synucleinopathies compared to age-matched healthy individuals. Various ANA HEp-2 patterns were identified, but no specific pattern was associated with individual synucleinopathies. We conclude hereby that synucleinopathies are not associated with detectable presence of ANA in plasma. [ABSTRACT FROM AUTHOR]

The immune system's amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains unclear. This study aims to assess if hospitalized COVID-19 patients face a worse prognosis based on ANA presence, even without autoimmune diseases. We performed a retrospective, single-center, observational cohort study, enrolling 638 COVID-19 patients hospitalized from April 2020 to March 2021 at Hospital "Policlinico Riuniti" of Foggia (Italy). COVID-19 patients with a positive ANA test exhibited a significantly lower 30-day survival rate (64.4% vs. 83.0%) and a higher likelihood of severe respiratory complications during hospitalization than those with negative ANA screening (35.4% vs. 17.0%) (p < 0.001). The association between poor prognosis and ANA status was identified by calculating the HALP score (Hemoglobin-Albumin-Lymphocyte-Platelet), which was lower in COVID-19 patients with a positive ANA test compared to ANA-negative patients (108.1 ± 7.4 vs. 218.6 ± 11.2 AU; p < 0.011). In detail, COVID-19 patients with a low HALP showed a lower 30-day survival rate (99.1% vs. 83.6% vs. 55.2% for high, medium, and low HALP, respectively; p < 0.001) and a higher incidence of adverse respiratory events compared to those with high and medium HALP (13.1% vs. 35.2% vs. 64.6% for high, medium, and low HALP, respectively; p < 0.001). In summary, ANA positivity in COVID-19 patients appears to be linked to a more aggressive disease phenotype with a reduced survival rate. Furthermore, we propose that the HALP score could serve as a valuable parameter to assess prognosis for COVID-19 patients. [ABSTRACT FROM AUTHOR]

Purpose: To report the uveitic manifestations of patients with systemic lupus erythematosus (SLE). Methods: This was a retrospective analysis of all SLE cases with ocular manifestations seen by a single ophthalmologist between 2015 and December 2021. Results: In total, seven patients with a median age of 40 (range 18-50) years were included in the study. Female (85.7%) predominance was noted. Ocular findings were bilateral in 71% (five patients) of cases. Majority (10 eyes, 83%) of the patients had retinal vasculitis as the common finding. Antinuclear antibodies were positive in all the patients. The vision improved in two (16.6%) eyes, was stable in eight (66%) eyes, and worsened in one (8%) eye. All the patients were treated with oral steroids along with immunosuppressive agents. Conclusion: Though SLE is rare cause of uveitis, it can be associated with significant ocular morbidity. Hence, early diagnosis and treatment can salvage vision in many cases. [ABSTRACT FROM AUTHOR]

Antinuclear antibodies (ANA) are a wide group of proteins directed against autologous cellular components, primarily nucleic acids and histones. Their levels are assessed using immunofluorescence on Hep-2 cells or a solid-phase ANA screening immunoassay to subsequently obtain titer value with positive cut-point of ≥1:80. Studies show that ANA can be found in 13% of general population, but typically they are associated with autoimmune conditions and inflammatory connective tissue diseases for example: systemic lupus erythematosus (SLE), sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, juvenile idiopathic arthritis, systemic sclerosis, inflammatory myopathies. ANA detection is especially important for SLE, where 2 antibody types - anti-Sm and anti-dsDNA - serve as an entry diagnostic criterion. With increasing patient screening for those antibodies, it is important to determine that alone, positive ANA assays cannot confirm nor deny any disease and to classify their presence as a marker of a disease it is required to satisfy additional additive criteria approved in 2019 by European League Against Rheumatism/American College of Rheumatology. SLE diagnosis can be made when patient collects 10 points from clinical or immunologic domains described by EULAR/ACR, which makes SLE diagnosis challenging and therefore, describing the guidelines is vital to remain cautious about overestimation of the position positive ANA values hold in clinical practice. In conclusion the positive ANA test may be a basis for diagnosis, when additional symptoms occur, but alone does not hold any diagnostic significance and may lead to unnecessary stress for patient.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, often affecting women of childbearing age, with periods of exacerbations and remissions. SLE can impact multiple organs, causing a range of clinical symptoms. Neuropsychiatric systemic lupus erythematosus (NPSLE) includes symptoms like headaches, seizures, anxiety disorders, cognitive dysfunctions, psychosis, and neuropathies. Its diagnosis is challenging, and treatment is complex. Purpose: This study aims to explain the pathophysiology of NPSLE, describe diagnostic methods, and summarize current treatment methods based on recent research. Methods: Databases such as PubMed, Medline, and ResearchGate were used. State of current knowledge: Early and accurate diagnosis of SLE is crucial for optimal patient management. The 2019 EULAR/ACR classification criteria have improved diagnostic precision with a weighted scoring system for diverse disease manifestations. Therapy of neuropsychiatric lupus focuses on symptom control and causal treatment, considering anti-inflammatory action or counteracting ischemic incidents. It involves immunosuppressive agents and antiplatelet or anticoagulant substances. Non-pharmacological interventions and lifestyle modifications are also important. The dynamic criteria reflect ongoing advancements in understanding SLE, emphasizing continuous research and collaboration. Conclusions: The diagnosis of NPSLE requires excluding other causes of neuropsychiatric symptoms, such as infections, endocrine disorders, or drug reactions. Diagnostic methods vary based on symptoms, including lumbar puncture, CSF analysis, EEG, cognitive function assessment, and MRI. The treatment of NPSLE focuses on symptom control and causal treatment, with therapy individualized based on symptom severity and patient burden.

Detection of specific antinuclear antibodies is very important in term of diagnosis, prognosis and management of patients with systemic autoimmune rheumatic diseases. Chemiluminescence microarray immunoassay (CLMIA) is a microdot array-based method that allows simultaneous detection of multiple antinuclear antibodies, which received increasing attention.

The pathophysiology of dengue may be influenced by antibodies released during infection. Several autoimmune diseases are accompanied by antinuclear antibodies (ANAs) but 8–10% of the general population have positive ANA tests. To test the hypothesis that an ANA-positive test indicates an immune dysregulated state that modifies the risk for certain clinical disorders in people with or without an autoimmune disease, we examined the various ANA profiles and their relationships to various autoimmune disorders, as well as the severity of these relationships, in patients infected with dengue fever. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) methods were used. Indirect immunofluorescence assay (IIFA) and line immunoassay (LIA) were performed to detect and differentiate the ANAs among dengue infected patients. Out of 135 dengue virus-positive patients, 94.07% were positive by ELISA and 5.93% positive by RT-PCR method. ANAs by IIFA and LIA were detected in 54.8% and 18.5% of the dengue positive patients, respectively, and 10.3% and 7.1% of the 126 dengue negative patients, respectively. This study showed that dengue was associated with an increased risk of autoimmune myositis and mixed connective tissue disease (MCTD), a rare complication of dengue. The risk of other autoimmune diseases did not seem to increase after DENV infection.

In 2019, the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) proposed new criteria to aid classify a patient with systemic lupus erythematosus. These criteria use a point-based system ranging from 2-10 points. The presence of antinuclear antibody is an entry criterion for classification. Sensitivity and specificity are 93% and 96%, respectively. Non-infectious fever was added as the new criterion. VDRL and LE cell tests and photosensitivity have been removed. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Although it is very uncommon, SLE may initially present with recurrent episodes of EM‐like rash. Despite the various possibilities underlying their association, prompt identification, and treatment of SLE in patients presenting with EM is important to prevent death or serious organ damage. Rowell's syndrome (RS) is an uncommon presentation of systemic lupus erythematosus (SLE) with erythema multiforme (EM)‐like lesions associated with specific serological changes, including positive rheumatoid factor (RF), speckled antinuclear antibody (ANA), positive rheumatoid factor, or anti‐La antibodies in the serum. Our case, a 41‐year‐old male, presented with features of EM. Upon investigation, we identified underlying systemic lupus erythematosus, marking a rare instance of SLE presenting for the first time as EM. Classical or true EM is precipitated by trigger factors such as infective agents like the herpes simplex virus, Mycoplasma pneumoniae, drugs like anticonvulsants, antibiotics, and non‐steroid anti‐inflammatory drugs, any underlying malignancy, or connective tissue disorders, and is not associated with any specific serological abnormalities. EM cases associated with LE lesions where an EM trigger factor is missing are considered an RS diagnostic criterion. In this case report, the importance of considering SLE in patients presenting initially with recurrent episodes of EM‐like rash is emphasized. RS should be considered, especially when there is no evidence of triggering factors. Early diagnosis and prompt treatment of SLE are crucial to preventing death and irreversible organ damage. [ABSTRACT FROM AUTHOR]

Objective: Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas for clinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. We developed and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals. Methods: Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples. Results: We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a diseasespecific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set. Conclusion: We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals. [ABSTRACT FROM AUTHOR]

Rare antinuclear antibody (ANA) pattern recognition has been a widely applied technology for routine ANA screening in clinical laboratories. In recent years, the application of deep learning methods in recognizing ANA patterns has witnessed remarkable advancements. However, the majority of studies in this field have primarily focused on the classification of the most common ANA patterns, while another subset has concentrated on the detection of mitotic metaphase cells. To date, no prior research has been specifically dedicated to the identification of rare ANA patterns. In the present paper, we introduce a novel attention-based enhancement framework, which was designed for the recognition of rare ANA patterns in ANA-indirect immunofluorescence images. More specifically, we selected the algorithm with the best performance as our target detection network by conducting comparative experiments. We then further developed and enhanced the chosen algorithm through a series of optimizations. Then, attention mechanism was introduced to facilitate neural networks in expediting the learning process, extracting more essential and distinctive features for the target features that belong to the specific patterns. The proposed approach has helped to obtained high precision rate of 86.40%, 82.75% recall, 84.24% F1 score and 84.64% mean average precision for a 9-category rare ANA pattern detection task on our dataset. Finally, we evaluated the potential of the model as medical technologist assistant and observed that the technologist's performance improved after referring to the results of the model prediction. These promising results highlighted its potential as an efficient and reliable tool to assist medical technologists in their clinical practice. [ABSTRACT FROM AUTHOR]

Antibodies to DNA are a diverse set of antibodies that bind sites on DNA, a polymeric macromolecule that displays various conformations. In a previous study, we showed that sera of normal healthy subjects (NHS) contain IgG antibodies to Z-DNA, a left-handed helix with a zig-zig backbone. Recent studies have demonstrated the presence of Z-DNA in bacterial biofilms, suggesting a source of this conformation to induce responses. To characterize further antibodies to Z-DNA, we used an ELISA assay with brominated poly(dGdC) as a source of Z-DNA and determined the isotype of these antibodies and their binding properties. Results of these studies indicate that NHS sera contain IgM and IgA as well as IgG anti-Z-DNA antibodies. As shown by the effects of ionic strength in association and dissociation assays, the anti-Z-DNA antibodies bind primarily by electrostatic interactions; this type of binding differs from that of induced anti-Z-DNA antibodies from immunized animals which bind by non-ionic interactions. Furthermore, urea caused dissociation of NHS anti-Z-DNA at molar concentrations much lower than those for the induced antibodies. These studies also showed IgA anti-Z-DNA antibodies in fecal water. Together, these studies demonstrate that antibodies to Z-DNA occur commonly in normal immunity and may arise as a response to Z-DNA of bacterial origin. [ABSTRACT FROM AUTHOR]

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown. Methods: TriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023. Exposure was defined as COVID-19 diagnosis (ICD-10 code or positive laboratory test). Age- and sex-propensity score-matched controls never had COVID-19 diagnosed. Outcomes were assessed 1 month to 1 year after the index date. Patients with AD prior to or within 1 month after the index date were excluded from the primary analysis. Incidence and risk ratios of each AD were assessed. Results: A total of 3,908,592 patients were included. Of 24 AD patients assessed, adjusted risk ratios for eight AD patients who had COVID-19 were higher compared to those who had no COVID-19. Cutaneous vasculitis (adjusted hazard ratio (aHR): 1.82; 95% CI 1.55-2.13), polyarteritis nodosa (aHR: 1.76; 95% CI 1.15-2.70), and hypersensitivity angiitis (aHR: 1.64; 95% CI 1.12-2.38) had the highest risk ratios. Overall, psoriasis (0.15%), rheumatoid arthritis (0.14%), and type 1 diabetes (0.13%) had the highest incidence during the study period, and of these, psoriasis and diabetes were more likely after COVID-19. The risk of any AD was lower if COVID-19 was diagnosed when Omicron variants were the predominant circulating strains. A positive antinuclear antibody was more likely and predictive of AD after COVID-19. Discussion: SARS-CoV-2 may be a potential trigger for some AD, but the risk for AD may decrease with time given the apparent lower risk after infection with Omicron variants. [ABSTRACT FROM AUTHOR]

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs' diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions. [ABSTRACT FROM AUTHOR]

Purpose: To report the uveitic manifestations of patients with systemic lupus erythematosus (SLE). Methods: This was a retrospective analysis of all SLE cases with ocular manifestations seen by a single ophthalmologist between 2015 and December 2021. Results: In total, seven patients with a median age of 40 (range 18–50) years were included in the study. Female (85.7%) predominance was noted. Ocular findings were bilateral in 71% (five patients) of cases. Majority (10 eyes, 83%) of the patients had retinal vasculitis as the common finding. Antinuclear antibodies were positive in all the patients. The vision improved in two (16.6%) eyes, was stable in eight (66%) eyes, and worsened in one (8%) eye. All the patients were treated with oral steroids along with immunosuppressive agents. Conclusion: Though SLE is rare cause of uveitis, it can be associated with significant ocular morbidity. Hence, early diagnosis and treatment can salvage vision in many cases.

Anti-DNA antibodies are known to be classical serological hallmarks of systemic lupus erythematosus (SLE). In addition to high-affinity antibodies, the autoantibody pool also contains natural catalytic anti-DNA antibodies that recognize and hydrolyze DNA. However, the specificity of such antibodies is uncertain. In addition, DNA binding to a surface such as the cell membrane, can also affect its recognition by antibodies. Here, we analyzed the hydrolysis of short oligodeoxyribonucleotides (ODNs) immobilized on the microarray surface and in solution by catalytic anti-DNA antibodies from SLE patients. It has been shown that IgG antibodies from SLE patients hydrolyze ODNs more effectively both in solution and on the surface, compared to IgG from healthy individuals. The data obtained indicate a more efficient hydrolysis of ODNs in solution than immobilized ODNs on the surface. In addition, differences in the specificity of recognition and hydrolysis of certain ODNs by anti-DNA antibodies were revealed, indicating the formation of autoantibodies to specific DNA motifs in SLE. The data obtained expand our understanding of the role of anti-DNA antibodies in SLE. Differences in the recognition and hydrolysis of surface-tethered and dissolved ODNs need to be considered in DNA microarray applications.

Rheumatoid arthritis (RA) is a common chronic, systemic autoimmune disease characterized by erosive arthritis, with a global prevalence of 0.25% to 1.00%, which may ultimately lead to joint deformity and loss of function. Antinuclear antibody (ANA) refers to auto-antibodies that target various components of eukaryotic cells. Although ANA may be frequently detected in RA patients, with a positive rate of 30% to 60%, the significance of ANA in the diagnosis and treatment of RA remains unclear. Nuclear patterns in RA population are dominated by speckled and homogeneous patterns, mainly at low titres. The detection rate of extractable nuclear antibodies is usually lower than that of ANA. The serum levels of rheumatoid factor and anti-cyclic citrullinated peptide antibody in ANA-positive RA patients are much higher than ANA-negative ones, and joint erosion of ANA-positive RA patients had more severe joint erosion on imaging as well. Therefore, ANA is a potential predictor of severe joint injury. ANA-positive RA patients are more likely to have extra-articular manifestations [such as subcutaneous nodules(82% vs 46%), ocular lesions(38% vs 6%), and infections(38% vs 12%)].In terms of RA comorbidities, compared to the ANA negative group, the ANA positive group had higher levels of moderate and severe anemia (16.04% vs 6.9%; 6.6% vs 0.07%), Sjogren's syndrome (19.5% vs 4.1%), and vasculitis (29% vs 7%). In addition, ANA positivity is an independent risk factor for elderly RA patients with carotid intimal thickening (HR=4.089) and adverse pregnancy outcomes in female RA (OR=3.268, P=0.045), respectively. Attention should be paid to high-titre ANA-positive RA patients for preventive measures. In terms of treatment, RA patients who are ANA-positive when given tumour necrosis factor-α inhibitor (TNFi) treatment got much poorer therapeutic response than ANA-negative ones, especially those with high titres were more prone to generating anti-drug antibodies. Increase of ANA titer induced by TNFi is associated with no response to TNFi treatment, thus monitoring the change of ANA may predict the long-term efficacy of TNFi. The most common adverse event of TNFi is drug-induced lupus. Although it has been confirmed that the induction of anti-double-stranded DNA antibodies is associated with poor efficacy of TNFi, large-scale studies are still needed to confirm the correlation between the increase of ANA titer or ocurence of dsDNA antibody and the induction of drug-induced lupus. In conclusion, this paper reviews the research progress on ANA characteristics in RA population, clinical manifestations of ANA-positive RA, and the association between ANA and TNFi prognosis. The potential of ANA as a new biomarker of RA needs to be further studied.

Introduction: The combination of patterns is a frequent and challenging situation in the daily laboratory routine of autoantibodies testing using HEp-2 cells indirect immunofluorescence assay (HEp-2-IFA). Recently, the Brazilian Consensus on Autoantibodies (BCA) named these combinations as complex patterns (CPs) and organized them into 3 subtypes: multiple, mixed, and composite. This study aimed to describe the most frequent combinations of HEp-2-IIF patterns according to this new nomenclature. Methods: Routine HEp-2-IFA results reported in January and June 2017 were reviewed using the new BCA classification. Visual pattern recognition was performed by experts on HEp-2-IFA readings, using the International Consensus on Antinuclear Antibodies (ANA) Patterns (ICAP) and BCA recommendations. Results: 54,990 serum samples from different patients were tested for ANAHEp-2, and 11,478 (20.9%) were positive at a titer ≥ 1/80. Among these positive samples, 1,111 (9.7%) displayed CPs, divided into 95 different combinations. A higher proportion of CPs was observed in the pediatric age group. Multiple, mixed, and composite patterns were present in 85.3, 5.4, and 9.5% of the samples, respectively. In the multiple/mixed pattern group (n=1,005), double, triple, and quadruple combinations (ICAP/BCA codes) were observed in 97.7%, 2.2%, and 0.1%, respectively. The double nuclear pattern was the most prevalent combination observed (67.6%). The most common CPs registered were AC-4 (nuclear fine speckled) + AC-6,7 (nuclear discrete dots) (n=264); AC-2 (nuclear dense fine speckled) + AC-6,7 (n=201); AC-4+AC-8,9,10 (nucleolar) (n=129); and AC-3 (centromere)+AC-4 (n=124). All of these combinations were in the multiple subgroup. Conclusion: Almost 10% of positive results in the HEp-2 procedure displayed CPs. Among the 3 subtypes of CPs proposed, the multiple pattern was the most prevalent, especially in the pediatric population. The AC-4, AC-2, and AC-6,7 were the most prevalent single patterns observed in the combinations described in this study. There was a significant association between age and the prevalence of most combined patterns. The AC-4+AC-6,7 combination was the most prevalent complex pattern detected regardless of the age group. The AC-2 +AC-6,7 was more prevalent in younger individuals. The concepts involved in the CPs definition should add value to the reading and interpretation of the HEp-2-IIF assay. [ABSTRACT FROM AUTHOR]

Simple Summary: Some autoimmune diseases have been linked to an increased risk of non-Hodgkin lymphoma (NHL), but the evidence varies across different subtypes of NHL, and few studies have examined whether autoimmunity is more generally associated with disease risk. Given the rise in autoimmunity, as measured by antinuclear antibodies (ANA) over time in the U.S., it is important to evaluate its potential association with NHL risk. In this nested case-control study, we measured ANA and other autoimmune biomarkers in serum collected years prior to diagnosis for cases and controls. We demonstrate that the presence of ANA is associated with an increased risk of diffuse large B-cell lymphoma, a common subtype of non-Hodgkin lymphoma. We further show that specific autoimmune biomarkers are associated with an increased risk of NHL, especially diffuse large B-cell and marginal zone lymphoma. Our study establishes autoimmunity as a risk factor for diffuse large B-cell lymphoma. Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88–1.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15–2.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18–7.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02–12.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26–62.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor. [ABSTRACT FROM AUTHOR]

Key Clinical Message Although it is very uncommon, SLE may initially present with recurrent episodes of EM‐like rash. Despite the various possibilities underlying their association, prompt identification, and treatment of SLE in patients presenting with EM is important to prevent death or serious organ damage. Abstract Rowell's syndrome (RS) is an uncommon presentation of systemic lupus erythematosus (SLE) with erythema multiforme (EM)‐like lesions associated with specific serological changes, including positive rheumatoid factor (RF), speckled antinuclear antibody (ANA), positive rheumatoid factor, or anti‐La antibodies in the serum. Our case, a 41‐year‐old male, presented with features of EM. Upon investigation, we identified underlying systemic lupus erythematosus, marking a rare instance of SLE presenting for the first time as EM. Classical or true EM is precipitated by trigger factors such as infective agents like the herpes simplex virus, Mycoplasma pneumoniae, drugs like anticonvulsants, antibiotics, and non‐steroid anti‐inflammatory drugs, any underlying malignancy, or connective tissue disorders, and is not associated with any specific serological abnormalities. EM cases associated with LE lesions where an EM trigger factor is missing are considered an RS diagnostic criterion. In this case report, the importance of considering SLE in patients presenting initially with recurrent episodes of EM‐like rash is emphasized. RS should be considered, especially when there is no evidence of triggering factors. Early diagnosis and prompt treatment of SLE are crucial to preventing death and irreversible organ damage.

ObjectivePositive antinuclear antibodies (ANAs) cause diagnostic dilemmas for clinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. We developed and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals.MethodsUsing a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples.ResultsWe assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set.ConclusionWe developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals.

IntroductionSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown.MethodsTriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023. Exposure was defined as COVID-19 diagnosis (ICD-10 code or positive laboratory test). Age- and sex-propensity score-matched controls never had COVID-19 diagnosed. Outcomes were assessed 1 month to 1 year after the index date. Patients with AD prior to or within 1 month after the index date were excluded from the primary analysis. Incidence and risk ratios of each AD were assessed.ResultsA total of 3,908,592 patients were included. Of 24 AD patients assessed, adjusted risk ratios for eight AD patients who had COVID-19 were higher compared to those who had no COVID-19. Cutaneous vasculitis (adjusted hazard ratio (aHR): 1.82; 95% CI 1.55–2.13), polyarteritis nodosa (aHR: 1.76; 95% CI 1.15–2.70), and hypersensitivity angiitis (aHR: 1.64; 95% CI 1.12–2.38) had the highest risk ratios. Overall, psoriasis (0.15%), rheumatoid arthritis (0.14%), and type 1 diabetes (0.13%) had the highest incidence during the study period, and of these, psoriasis and diabetes were more likely after COVID-19. The risk of any AD was lower if COVID-19 was diagnosed when Omicron variants were the predominant circulating strains. A positive antinuclear antibody was more likely and predictive of AD after COVID-19.DiscussionSARS-CoV-2 may be a potential trigger for some AD, but the risk for AD may decrease with time given the apparent lower risk after infection with Omicron variants.

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

Abstract Background Antinuclear antibodies (ANA) are antibodies present in several autoimmune disorders. However, a large proportion of the general population (20%) also have a positive test; very few of these individuals will develop an autoimmune disease, and the clinical impact of a positive ANA in them is not known. Thus, we test the hypothesis that ANA + test reflects a state of immune dysregulation that alters risk for some clinical disorders in individuals without an autoimmune disease. Methods We performed high throughput association analyses in a case–control study using real world data from the de-identified electronic health record (EHR) system from Vanderbilt University Medical Center. The study population included individuals with an ANA titer ≥ 1:80 at any time (ANA +) and those with negative results (ANA-). The cohort was stratified into sub-cohorts of individuals with and without an autoimmune disease. A phenome-wide association study (PheWAS) adjusted by sex, year of birth, race, and length of follow-up was performed in the study cohort and in the sub-cohorts. As secondary analyses, only clinical diagnoses after ANA testing were included in the analyses. Results The cohort included 70,043 individuals: 49,546 without and 20,497 with an autoimmune disease, 26,579 were ANA + and 43,464 ANA-. In the study cohort and the sub-cohort with autoimmune disease, ANA + was associated (P ≤ 5 × 10–5) with 88 and 136 clinical diagnoses respectively, including lupus (OR ≥ 5.4, P ≤ 7.8 × 10–202) and other autoimmune diseases and complications. In the sub-cohort without autoimmune diseases, ANA + was associated with increased risk of Raynaud’s syndrome (OR ≥ 2.1) and alveolar/perialveolar-related pneumopathies (OR ≥ 1.4) and decreased risk of hepatitis C, tobacco use disorders, mood disorders, convulsions, fever of unknown origin, and substance abuse disorders (OR ≤ 0.8). Analyses including only diagnoses after ANA testing yielded similar results. Conclusion A positive ANA test, in addition to known associations with autoimmune diseases, Raynaud’s phenomenon, and idiopathic fibrosing alveolitis related disorders, is associated with decreased prevalence of several non-autoimmune diseases.

The immune system’s amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains unclear. This study aims to assess if hospitalized COVID-19 patients face a worse prognosis based on ANA presence, even without autoimmune diseases. We performed a retrospective, single-center, observational cohort study, enrolling 638 COVID-19 patients hospitalized from April 2020 to March 2021 at Hospital “Policlinico Riuniti” of Foggia (Italy). COVID-19 patients with a positive ANA test exhibited a significantly lower 30-day survival rate (64.4% vs. 83.0%) and a higher likelihood of severe respiratory complications during hospitalization than those with negative ANA screening (35.4% vs. 17.0%) (p < 0.001). The association between poor prognosis and ANA status was identified by calculating the HALP score (Hemoglobin-Albumin-Lymphocyte-Platelet), which was lower in COVID-19 patients with a positive ANA test compared to ANA-negative patients (108.1 ± 7.4 vs. 218.6 ± 11.2 AU; p < 0.011). In detail, COVID-19 patients with a low HALP showed a lower 30-day survival rate (99.1% vs. 83.6% vs. 55.2% for high, medium, and low HALP, respectively; p < 0.001) and a higher incidence of adverse respiratory events compared to those with high and medium HALP (13.1% vs. 35.2% vs. 64.6% for high, medium, and low HALP, respectively; p < 0.001). In summary, ANA positivity in COVID-19 patients appears to be linked to a more aggressive disease phenotype with a reduced survival rate. Furthermore, we propose that the HALP score could serve as a valuable parameter to assess prognosis for COVID-19 patients.

IntroductionThe combination of patterns is a frequent and challenging situation in the daily laboratory routine of autoantibodies testing using HEp-2 cells indirect immunofluorescence assay (HEp-2-IFA). Recently, the Brazilian Consensus on Autoantibodies (BCA) named these combinations as complex patterns (CPs) and organized them into 3 subtypes: multiple, mixed, and composite. This study aimed to describe the most frequent combinations of HEp-2-IIF patterns according to this new nomenclature.MethodsRoutine HEp-2-IFA results reported in January and June 2017 were reviewed using the new BCA classification. Visual pattern recognition was performed by experts on HEp-2-IFA readings, using the International Consensus on Antinuclear Antibodies (ANA) Patterns (ICAP) and BCA recommendations.Results54,990 serum samples from different patients were tested for ANA-HEp-2, and 11,478 (20.9%) were positive at a titer ≥ 1/80. Among these positive samples, 1,111 (9.7%) displayed CPs, divided into 95 different combinations. A higher proportion of CPs was observed in the pediatric age group. Multiple, mixed, and composite patterns were present in 85.3, 5.4, and 9.5% of the samples, respectively. In the multiple/mixed pattern group (n=1,005), double, triple, and quadruple combinations (ICAP/BCA codes) were observed in 97.7%, 2.2%, and 0.1%, respectively. The double nuclear pattern was the most prevalent combination observed (67.6%). The most common CPs registered were AC-4 (nuclear fine speckled) + AC-6,7 (nuclear discrete dots) (n=264); AC-2 (nuclear dense fine speckled) + AC-6,7 (n=201); AC-4+AC-8,9,10 (nucleolar) (n=129); and AC-3 (centromere)+AC-4 (n=124). All of these combinations were in the multiple subgroup.ConclusionAlmost 10% of positive results in the HEp-2 procedure displayed CPs. Among the 3 subtypes of CPs proposed, the multiple pattern was the most prevalent, especially in the pediatric population. The AC-4, AC-2, and AC-6,7 were the most prevalent single patterns observed in the combinations described in this study. There was a significant association between age and the prevalence of most combined patterns. The AC-4+AC-6,7 combination was the most prevalent complex pattern detected regardless of the age group. The AC-2+AC-6,7 was more prevalent in younger individuals. The concepts involved in the CPs definition should add value to the reading and interpretation of the HEp-2-IIF assay.

Introduction: Antinuclear antibodies (ANAs) are regarded as a hallmark of connective tissue diseases (CTDs) and play a key role in their diagnosis, but the value of some particular antibodies in management of patients and the disease prognosis is controversial. The mechanism underlying the production of ANAs in CTDs, other chronic inflammatory conditions and even in healthy people, is not completely elucidated. Anti‐DFS70 antibodies connected with the dense fine speckled autoantigen of 70 kD, known as the lens epithelium‐derived growth factor p75, are a subgroup of ANAs. Their presence and coexistence with other antibodies and their clinical significance are the matter of debate. Methods: Based on literature data, the authors focused on current knowledge explaining the role of anti‐DFS70 antibodies in selected CTDs. Results: However, the literature data is ambiguous and does not fully support the validity of the anti‐DFS70 assay for a specific CTD diagnosis. Most researchers claim that the presence of anti‐DFS70 as the only one usually exclude the diagnosis of CTD. Nevertheless, its coexistence with other ANAs is not an excluding factor but has predictive value due to more favorable course of CTD. Such situations may also suggest an enhanced risk of the development of a CTD in the future. Conclusions: Although more studies are needed in this field, it seems reasonable to ascertain the presence of anti‐DFS70 in routine clinical practice. [ABSTRACT FROM AUTHOR]

(1) Background: Non-Hodgkin Lymphoma is a neoplasm that can significantly compromise the immune system, but timely assessment can change the patient outcome. In cancer, the activation of the immune system could lead to the secretion of autoantibodies. (2) Methods: A retrospective cohort study was performed from 2017 to 2019 in patients with Non-Hodgkin Lymphoma diagnosed with a biopsy. (3) Results: We included 39 patients who were newly diagnosed, untreated, and without any autoimmune disease previously reported. Thirty patients had the presence of autoantibodies (antiphospholipid antibodies, anti-cytoplasmic neutrophils antibodies, antinuclear antibodies), and nine were without autoantibodies. There were no statistical differences among groups regarding clinical, demographic, staging, and prognosis characteristics. Also, there were no differences in the outcomes of the patients after finishing chemotherapy and one year after initiating treatment. (4) Conclusions: Further investigations must be conducted regarding an extended panel of autoantibodies because the panel of autoantibodies in this study did not show a relationship between the presence and the clinical outcome of the patients. [ABSTRACT FROM AUTHOR]

The relevance of the problem of immunoinflammatory rheumatic diseases (IIRD) for modern medicine is determined by their high prevalence in the population, the difficulty of early diagnosis, the rapid development of disability and poor life prognosis. Recent data on the significance of anti-DFS70 have opened up new possibilities for optimizing the step-by-step diagnosis of IIRD. The detection of these antibodies can help in the interpretation of a positive result for antinuclear antibodies (ANA) by indirect immunofluorescence assay on HEp-2 cells (IIFA-HEp-2) in the absence of autoantibodies specific for IIRD. Detection of anti-DFS70 in antinuclear factor (ANF) seropositive patients without clinical and/or serological markers characteristic of a certain disease from the IIRD group can be considered as a potential marker that excludes this group of diseases.

Antibodies to DNA are a diverse set of antibodies that bind sites on DNA, a polymeric macromolecule that displays various conformations. In a previous study, we showed that sera of normal healthy subjects (NHS) contain IgG antibodies to Z-DNA, a left-handed helix with a zig-zig backbone. Recent studies have demonstrated the presence of Z-DNA in bacterial biofilms, suggesting a source of this conformation to induce responses. To characterize further antibodies to Z-DNA, we used an ELISA assay with brominated poly(dGdC) as a source of Z-DNA and determined the isotype of these antibodies and their binding properties. Results of these studies indicate that NHS sera contain IgM and IgA as well as IgG anti-Z-DNA antibodies. As shown by the effects of ionic strength in association and dissociation assays, the anti-Z-DNA antibodies bind primarily by electrostatic interactions; this type of binding differs from that of induced anti-Z-DNA antibodies from immunized animals which bind by non-ionic interactions. Furthermore, urea caused dissociation of NHS anti-Z-DNA at molar concentrations much lower than those for the induced antibodies. These studies also showed IgA anti-Z-DNA antibodies in fecal water. Together, these studies demonstrate that antibodies to Z-DNA occur commonly in normal immunity and may arise as a response to Z-DNA of bacterial origin.

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs’ diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions.

Background: Brief erythematous-papular skin rashes suggest the diagnosis of urticaria; However, it may be another type of dermatitis, and complementary examinations must be carried out to establish its diagnosis. Case report: 53-year-old female patient, diagnosed in 2016 with diffuse large B cell lymphoma, in complete remission. Since 2010, he has had episodes of erythematous-papular lesions lasting 24-36 hours. He received antihistamines, corticosteroids and omalizumab without clinical improvement. The ANA determination was positive (1/320), nuclear mitotic pattern. The skin biopsy was compatible with dermatitis herpetiformis. The study of celiac and locus antibodies showed positivity for HLA-DQ2 and DQ2.5 in heterozygosity. The diagnosis of dermatitis herpetiformis was established. Treatment consisted of a gluten-free diet and prescription of dapsone, with satisfactory results. Conclusion: It is important to establish the differential diagnosis of patients with chronic urticaria who do not respond to the reference treatment, in addition to carrying out a thorough clinical examination and physical examination before starting treatment and relying on a multidisciplinary team to establish an accurate diagnosis and treatment. appropriate. Due to the side effects of dapsone, subsequent follow-up of patients is essential. [ABSTRACT FROM AUTHOR]

Abstract Introduction Antinuclear antibodies (ANAs) are regarded as a hallmark of connective tissue diseases (CTDs) and play a key role in their diagnosis, but the value of some particular antibodies in management of patients and the disease prognosis is controversial. The mechanism underlying the production of ANAs in CTDs, other chronic inflammatory conditions and even in healthy people, is not completely elucidated. Anti‐DFS70 antibodies connected with the dense fine speckled autoantigen of 70 kD, known as the lens epithelium‐derived growth factor p75, are a subgroup of ANAs. Their presence and coexistence with other antibodies and their clinical significance are the matter of debate. Methods Based on literature data, the authors focused on current knowledge explaining the role of anti‐DFS70 antibodies in selected CTDs. Results However, the literature data is ambiguous and does not fully support the validity of the anti‐DFS70 assay for a specific CTD diagnosis. Most researchers claim that the presence of anti‐DFS70 as the only one usually exclude the diagnosis of CTD. Nevertheless, its coexistence with other ANAs is not an excluding factor but has predictive value due to more favorable course of CTD. Such situations may also suggest an enhanced risk of the development of a CTD in the future. Conclusions Although more studies are needed in this field, it seems reasonable to ascertain the presence of anti‐DFS70 in routine clinical practice.

Background: Erdheim-Chester disease is a form of histiocytosis. It is an extremely rare illness. Since its discovery, hundreds of cases of this disease have been identified across the globe. Pathologically, the condition is characterized by proliferation of lipid-rich foam-like tissue cells, which is especially prevalent in bones. Approximately 50% of patients develop infiltration into organs other than the bones. Case description: A patient with fever and bone pain is described in this case report. After visiting multiple hospitals and departments, undergoning battery of investigations, and ruling out other diseases, the patient was pathologically diagnosed with Erdheim-Chester disease after a biopsy of the associated bone destruction. The condition improved with symptomatic therapy. Conclusion: Numerous clinical symptoms make non-Langerhans cell histiocytosis challenging to diagnose and requires pathological diagnosis. Patients with unexplained multiple bone destruction must be alert against this disease from a clinical standpoint.

Sjögren's syndrome is a systemic autoimmune disease characterized by dry eyes and mouth due to the involvement of exocrine glands. However, it can manifest with GI symptoms that cover a broad spectrum from esophageal and intestinal dysmotility, achalasia, hypochlorhydria, and chronic atrophic gastritis to pancreatic enzyme deficiency, biliary dysfunction, and liver cirrhosis, which varies in its clinical manifestations and is often associated with erroneous approaches. This article reviews the GI manifestations of Sjögren's syndrome. It presents the case of a woman in her eighth decade of life with this syndrome. She showed asymptomatic hepatobiliary disease, documented abnormalities in liver profile tests, and a subsequent diagnosis of primary sclerosing cholangitis, for which she received initial treatment with ursodeoxycholic acid. During her condition, the patient has had three episodes of cholangitis, requiring endoscopic retrograde cholangiopancreatography with no findings of stones, with scant biliary sludge and discharge of purulent bile precipitated by her underlying liver disease. The association between Sjögren's syndrome and primary sclerosing cholangitis is rare and calls for special consideration. [ABSTRACT FROM AUTHOR]

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Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting multiple organs with different degrees of severity. SLE is typically diagnosed based on the presence of antinuclear antibodies (ANA) in the serum. However, seronegative SLE is rare and is diagnosed by clinicians when the patient's ANA is negative but fulfills other diagnostic criteria. Case report: We report a case of a 15-year-old South Asian female with SLE who had negative antinuclear antibodies yet displayed the typical clinical presentations of photosensitive maculopapular rash, joint pain, alopecia, anemia, and thrombocytopenia. Clinical evaluations in conjunction with lab results were used to establish a diagnosis of ANA-negative SLE. Conclusion: ANA positivity is an entry criterion for SLE; rarely, cases of ANA-negative SLE may present. A typical clinical presentation may help determine the diagnosis in such a scenario. However, still, the physician should rule out immunodeficiency and other systemic illnesses before reaching a diagnosis of ANA-negative pediatric SLE. [ABSTRACT FROM AUTHOR]

Background: The autoimmune response may be one of the causative factors for oral submucous fibrosis (OSMF). Serum levels of antinuclear antibodies (ANAs), anti-smooth muscle antibodies (ASMAs), and antithyroid microsomal antibodies (ATMAs) were evaluated in patients with and without OSMF. Objectives: This study aimed to evaluate the presence of autoantibodies in patients suffering from OSMF and those without it and compare both groups for ANAs, ATMAs, and ASMAs. Materials and Methods: The participants were 70 subjects with an age group of 18–80 years. Thirty-five patients with the diagnosis of OSMF were assigned to the case group, while 35 subjects without any OSMF were assigned to the control group. Serum samples were collected from the subjects and screened for serum autoantibodies (ANAs, ASMAs, and ATMAs) by indirect immune fluorescence. Results: In the case group, most of the patients were positive for ANAs and none were positive for ASMAs. ANA positivity was found to be more significant (P < 0.001) than ATMAs and ASMAs in both groups. While 10% of patients in the control group were positive for ATMAs, the control group showed negative status for both ANAs and ASMAs. There was a male predominance with the prevalence of ANAs. Conclusion: The study suggested a possible role of autoimmune response in OSMF.

Background: Pregnancy is associated with biochemical alterations and may be compounded by human immunodeficiency virus (HIV) infection potentially affecting pregnancy outcome. Aims: This study evaluated some biochemical parameters that could possibly affect pregnancy outcomes in HIV-infected women. Patients, Materials and Methods: The study involved 136 HIV sero-positive on highly active antiretroviral therapy (HAART) and 137 HIV sero-negative pregnant women, recruited from the Antenatal Clinic of Nnamdi Azikiwe University Teaching Hospital, Nnewi. Antinuclear antibodies (ANAs), anti-beta 2-glycoprotein-1 (βGP1), and thyroid peroxidase autoantibody (TPOab) were analysed using the enzyme-linked immunosorbent assay methods. Results: TPOab in HIV sero-positive subjects (104.9 ± 51.06 IU/mL) was significantly higher (P > 0.05) compared with controls (89.5 ± 33.5 IU/mL). ANA and βGP1 in test group (0.89 ± 0.31; 12.94 ± 8.9, respectively) did not change significantly (P > 0.05) compared with the controls (0.84 ± 0.27; 10.37 ± 9.6, respectively). There were no significant changes in measured biochemical parameters between trimesters (P > 0.05). Furthermore, there were no significant differences in measured biochemical parameters between subjects with different APGAR scores in all subject groups. Conclusion: HIV infection affected TPOab level but had no impact on ANA, βGP1, and APGAR score in HIV pregnancy under HAART.

BACKGROUND: Therapeutic plasma exchange (TPE) has been advocated as an adjunct to steroids and cytotoxic drugs in treating patients suffering from vasculitis and presenting with active disease, but we still have insufficient evidence on its effectiveness in improving the clinical response, especially in India. This study was planned to study the clinical outcome in severe vasculitic presentations treated with TPE as an adjunctive therapy. MATERIALS AND METHODS: A retrospective analysis of TPE procedures performed from July 2013 to July 2017 in the department of transfusion medicine at a large tertiary care hospital was done. All consecutive patients admitted with new diagnosis of systemic vasculitis presenting with active disease and severe presentations such as advanced renal failure or severe respiratory abnormalities or life-threatening vasculitis affecting the gastrointestinal tract, neurological and musculoskeletal system; who needed TPE for removal of preformed antibodies, were included in the study. RESULTS: There were a total of 31 patients in whom TPE was performed for severe systemic vasculitis; 26 adults and five pediatric. Six patients tested positive for perinuclear fluorescence, 13 for cytoplasmic fluorescence (cANCA), two for atypical antineutrophil cytoplasmic autoantibody, seven for anti-glomerular basement membrane antibodies, two for antinuclear antibodies (ANA), and one patient tested positive for ANA as well as cANCA before the augmentation of TPE. Out of 31, seven patients showed no clinical improvement and succumbed to the disease. At the end of desired number of procedures, 19 tested negative and five tested weak positive for their respective antibodies. CONCLUSION: Favorable clinical outcomes were observed with TPE in patients with antibody-positive systemic vasculitis.

Abstract Background Although antinuclear antibodies (ANAs), anti‐SSA and anti‐Ro52, are present in immunoglobulin preparations, it is unknown whether intravenous immunoglobulin (IVIG) therapy influences the testing of serum autoantibodies in patients with connective tissue diseases (CTDs). The present study aimed to investigate the dynamic change over time of serum ANA‐related autoantibodies in patients with CTDs receiving IVIG therapy. Methods Serum ANA‐related autoantibodies were monitored in two patients with CTD before IVIG therapy and at different times after therapy. These autoantibodies were tested in different batches of immunoglobulin preparations from seven pharmaceutical companies. Results One patient developed a new ANA pattern (cytoplasmic dense fine speckled pattern, AC‐19) just after IVIG therapy. Both patients developed de novo positivity for AMA‐M2 and anti‐SSA, but returned negative 1 month after IVIG therapy. The residual liquid in patients' immunoglobulin preparations showed positive ANAs with a high titer of AC‐19 (1:640), a low titer of the nuclear fine speckled pattern (AC‐4, 1:80), positive AMA‐M2, and positive anti‐SSA. ANA‐related autoantibodies were tested in 16 batches of immunoglobulin preparations and all had positive ANAs with two patterns: AC‐19 (1:640 or 1:320) and AC‐4 (1:80). AMA‐M2 and anti‐SSA were positive in 100% of the batches. Conclusion Our study highlights high‐titer AMA‐M2 autoantibodies in immunoglobulin preparations and suggests their transient transfer into a patient's circulation via IVIG therapy. To avoid incorrect clinical decisions based on postinfusion antibody titers, our data recommend retesting 1–2 months after high‐dose IVIG immunomodulatory treatment.

Abstract Symptoms of Wilson disease (WD) vary and additional factors such as autoimmunity may play an important role in WD pathogenesis. The presence of antinuclear antibodies (ANA), anti‐neutrophil cytoplasmic antibodies, neuronal surface antibodies, and onconeural antibodies in WD was investigated using standardized indirect immunofluorescence assays and Western Blot analysis. The presence of all studied autoantibodies was higher in WD patients in comparison to healthy subjects, but there was no statistically significant difference in autoantibodies frequency according to disease manifestation. D‐penicillamine treatment was associated with a higher presence of ANA than zinc sulfate but without an increase in autoimmune diseases rate.

Abstract Background The prevalence of anti-cell autoantibodies detected by indirect immunofluorescence assay on HEp-2 cells (HEp-2-IIFA) increases with age and is higher in female sex. The number of medical specialties that use HEp-2-IIFA in the investigation of autoimmune diseases has increased lately. This study aimed to determine the prevalence and patterns of autoantibodies on HEp-2-IIFA according to demographics variables and referring medical specialties. Methods A retrospective analysis of the HEp-2-IIFA carried out between January and June of 2017 was performed. The International Consensus on Antinuclear Antibodies Patterns (ICAP) and the Brazilian Consensus on Autoantibodies were used for patterns definition on visual reading of the slides. Anti-cell (AC) codes from ICAP and Brazilian AC codes (BAC) were used for patterns classification. Results From 54,990 samples referred for HEp-2-IIF testing, 20.9% were positive at titer ≥ 1/80. HEp-2-IIFA positivity in females and males was 24% and 12%, respectively (p

Abstract Anti‐TNFα inhibitor‐induced Lupus (ATIL) is a rare syndrome characterized by a wide array of symptoms ranging from skin manifestations to organ‐specific symptoms such as pleural effusions, pericardial effusions, hepatotoxicity, etc. Infliximab is implicated in most cases, and ATIL usually develops between the first month and 4 years of infliximab application. In this report, we present an interesting case of ATIL that developed rather gradually upon anti‐TNFa used to treat Crohn's disease. The patient presented with oral ulcers, photosensitive rash, diffuse alopecia, inflammation of the hands, and pleuritic chest pain. Comprehensive serological testing revealed the presence of antinuclear antibodies and anti‐DNA antibodies. During the evaluation, the patient developed headaches, followed by a brain MRI that suggested nonspecific white matter lesions. Given the chronic development of symptoms, invasive examinations such as an arteriogram were performed to exclude CNS vasculitis, which showed no evidence of the vasculitis. Therefore, in the absence of any clear radiographical signs of vasculitis, patients should not undergo invasive studies, including an angiogram. The CNS angiogram can be associated with several side effects, including damage to the blood vessel, bruising or bleeding at the puncture site, and infection, which can further aggravate ATIL. Although rare, ATIL should always be considered while evaluating a patient with suggestive symptoms on infliximab therapy. Further research on identifying the variety of clinical presentations of ATIL and the underlying pathophysiology can help improve health policy and clinical practice by reducing unnecessary examination and allowing early management and better‐quality care.

Background:Empirical use of Hydroxychloroquine (HCQ) in patients with positive antinuclear antibody spectrum (ANAs) test result is controversial regarding its impact on improving perinatal outcomes. This study aimed to investigate the effect of HCQ on adverse pregnancy outcomes associated with placental dysfunction in ANAs-positive patients.Methods:The study included pregnant women with positive ANAs test result from 2016 to 2020 in our center, and divided into a weakly positive and a positive group in just ANA positive patients among them. Univariate and multivariate analyses were conducted to determine the effect of HCQ on pregnancy outcomes in each subgroup. Stratified and interactive analyses were performed to assess the value of HCQ in improving pregnancy outcomes.Results:(i) A total of 261 cases were included, accounting for 30.60% of pregnancy complicated with autoimmune abnormalities, and 65.12% of them used HCQ during pregnancy. (ii) The application of HCQ significantly reduced the incidence of early-onset preeclampsia (1.18% vs. 12.09%, p = 0.040) and small-for-gestational-age infants (10.06% vs. 25.84%, p = 0.003) in the ANAs-positive population, increased birth weight (3075.87 ± 603.91 g vs. 2847.53 ± 773.73 g, p = 0.025), and prolonged gestation (38.43 ± 2.31 vs. 36.34 ± 5.45 weeks, p

Progressive pulmonary fibrosis is generally diagnosed when interstitial lung disease progression occurs in the absence of any other cause, and a subset of patients with myositis and associated interstitial lung disease may develop progressive pulmonary fibrosis. Numerous autoantibodies (e.g., against tRNA-synthetase, MDA5, Ro52) increase the risk of this clinical feature in myositis and we speculate that serum biomarkers, sought using the most sensitive laboratory techniques available (i.e., immunoprecipitation) may predict pulmonary involvement and allow the early identification of progressive pulmonary fibrosis. We herein provide a narrative review of the literature and also present original data on pulmonary fibrosis in a cohort of patients with myositis and serum anti-Ro52 with interstitial lung disease. Our results fit into the previous evidence and support the association between anti-Ro52 and signs of pulmonary fibrosis in patients with inflammatory myositis. We believe that the combination of available and real-life data has significant clinical relevance as a paradigm of serum autoantibodies that prove useful in determining precision medicine in rare connective tissue diseases.