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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]

Copyright of Revista de la Facultad de Medicina Humana is the property of Instituto de Investigaciones en Ciencias Biomedicas de la Universidad Ricardo Palma and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Detection of antinuclear antibodies (ANA) by indirect immunofluorescence assay using HEp-2 cells (HEp-2 IFA) is used to screen for various autoimmune diseases. HEp-2 IFA suffers from variability, which hampers harmonization. A questionnaire was developed to collect information on HEp-2 IFA methodology, computer-assisted diagnosis (CAD) systems, training, inter-observer variability, quality assessment, reagent lot change control, and method verification. The questionnaire was distributed to laboratories by Sciensano (Belgium), national EASI groups (Italy, Croatia, Portugal, Estonia, Greece) and ICAP (worldwide). Answers were obtained by 414 laboratories. The results were analysed in the framework of the recent EFLM/EASI/ICAP ANA recommendations (companion paper). Laboratories used either HEp-2, HEp-2000, or HEp-20-10 cells and most laboratories (80%) applied the same screening dilution for children and adults. The conjugate used varied between laboratories [IgG-specific (in 57% of laboratories) vs. polyvalent]. Sixty-nine percent of CAD users reviewed the automatic nuclear pattern and 53% of CAD users did not fully exploit the fluorescence intensity for quality assurance. Internal quality control was performed by 96% of the laboratories, in 52% of the laboratories only with strongly positive samples. Interobserver variation was controlled by 79% of the laboratories. Limited lot-to-lot evaluation was performed by 68% of the laboratories. Method verification was done by 80% of the respondents. Even though many laboratories embrace high-quality HEp-2 IFA, substantial differences in how HEp-2 IFA is performed and controlled remain. Acting according to the EFLM/EASI/ICAP ANA recommendations can improve the global performance and quality of HEp-2 IFA and nurture harmonization. [ABSTRACT FROM AUTHOR]

Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA). A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP). In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations. These recommendations are an important step to achieve high quality ANA testing. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the clinical significance of anti‐rods and rings (anti‐RR) antibodies in antinuclear antibodies (ANAs) test samples retrospectively. The laboratory data and clinical details of patients with positive anti‐RR antibodies were collected and analysed between December 2017 and May 2022 in the First Affiliated Hospital of Dalian Medical University. A total of 72 665 patients were tested for ANAs. There were 45 632 patients discovered with positive ANAs (62.80%), only 131 patients presented with anti‐RR antibodies (0.18%), among which only 68 patients were hospitalized patients with a definitive diagnosis. Among the 68 patients with a definitive diagnosis, 8 of 68 (11.8%) had autoimmune diseases, and 19 of 68 (27.9%) had renal diseases. Other diseases included liver disease, pulmonary disease, cerebral ischemia, cerebral infarction, chronic cardiac failure and venous thromboembolism. The detection rate of high titre(≥1:1000) anti‐RR antibodies is significantly higher in autoimmune diseases. [ABSTRACT FROM AUTHOR]

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: Systemic lupus erythematosus (SLE) is a disorder with a complex immunopathogenesis. It is well known that the disease begins with immunological alterations and autoantibody appearance in the serum years before clinical onset. As SLE has a strong tendency to familial aggregation, first‐degree relatives (FDRs) constitute a group at elevated risk. The current understanding is that external risk factors trigger underlying immune dysregulations, leading to overt disease in those with elevated genetic risk. Objective: This cross‐sectional study investigates the degree to which clinical features, external risk factors, and immunological profiles differ in SLE FDRs from healthy individuals and SLE patientts. Methods: Three groups were studied: Lupus patient FDRs (n = 56), healthy controls (n = 20), and SLE patients (n = 20). FDRs and healthy participants completed a detailed clinical questionnaire that included questions regarding smoking and estrogen drug history. All participants were tested for the presence of the following antinuclear autoantibodies (ANAs) against: nRNP/Sm, Sm, Ro60, Ro‐52, La, Scl‐70, PM‐Scl, PM‐ Scl, Jo‐1, CENP B, PCNA, dsDNA, nucleosomes, histones, RibP, AMA M2, DFS70, and eight soluble cytokines, including transforming growth factor‐β (TGF‐β), vitamin D levels, and antibodies against Epstein‐Barr virus (EBV). Results: Compared with the healthy controls, FDRs had higher titers of ANA, more specific staining immunofluorescent patterns, and more autoantibody specificities. Furthermore, FDRs differed significantly in their TGF‐β levels from the other two groups. In FDRs, some clinical features (hair loss, skin, and oral ulcer‐like lesions) were associated with higher ANA titers and some (oral ulcer‐like lesions) with the anti‐Ro60‐specific antibody. Interestingly, there was an association between ANA titers and levels of antibodies against EBV only in the FDR group. Conclusion: First‐degree relatives display unique clinical and immunological profiles, placing them between healthy individuals and SLE patients, with a balance between compensated immune dysregulation and disease‐developing potential. A possible association between ANA titer and the number of clinical complaints is observed, which needs to be confirmed in more extensive studies. [ABSTRACT FROM AUTHOR]

In patients with humoral autoimmune diseases antinuclear antibodies (ANAs) and joint pain are commonly found.[3] In this study, we aimed to provide insight into ANA development during dupilumab treatment in AD patients. Keywords: antinuclear antibodies; atopic dermatitis; autoimmunity; dupilumab; enthesitis; inflammatory arthritis EN antinuclear antibodies atopic dermatitis autoimmunity dupilumab enthesitis inflammatory arthritis 582 585 4 05/10/23 20230501 NES 230501 Key messages Dupilumab-associated muscle and/or joint pain is frequently reported as a side effect in atopic dermatitis patients. During dupilumab treatment only two patients switched from ANA negative to positive after 107 and 109 weeks of dupilumab treatment, respectively, of which one patient was previously diagnosed with rheumatoid arthritis (Table 2). [Extracted from the article]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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

• There is not a single specific laboratory marker to diagnose or exclude AIH. • Therefore, diagnosis of AIH is in most cases challenging for physicians. • Antibodies detection is mandatory even though not pathognomonic for AIH diagnosis. • Assessment of autoimmune serology in strict adherence to guidelines is essential. • IgG increase and autoimmunity background support an in-depth serological assessment. Diagnosis of autoimmune hepatitis (AIH) is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the disease. The clinical spectrum of AIH varies from completely asymptomatic to acute-severe or even rarely fulminant hepatic failure, while everybody can be affected irrespective of age, gender, and ethnicity. The old revised and the newer simplified diagnostic scores have been established by the International Autoimmune Hepatitis Group (IAIHG) in 1999 and 2008, respectively, which are based on several clinical, laboratory and histological parameters. Additionally, a thorough differential diagnosis from other diseases mimicking AIH is absolutely indicated. In this context, autoantibodies detection in patients with suspected AIH is mandatory -even though not pathognomonic- not only for AIH diagnosis but furthermore, for AIH classification (AIH-type 1 and AIH-type 2). Although autoimmune serology can be supportive of AIH diagnosis in ≥95% of cases if testing has been performed according to the IAIHG guidelines, this is not the case under real-life circumstances in routine clinical laboratories. Clinicians should be careful both for the importance of the required testing and how to interpret the results and therefore, they should communicate and discuss with the laboratory personnel to achieve the maximum benefit for the patient. Herein, a detailed and updated review of the diagnostic work-up for AIH diagnosis under real-life conditions is given to minimize the underestimation and misdiagnosis of AIH which can result in progression of the disease and unfavourable outcomes. [ABSTRACT FROM AUTHOR]

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.

Background: We previously evaluated blood screening data, including antinuclear antibodies (ANA), before initiating biologic treatment for patients with psoriasis in a real-world setting. However, we did not analyze change in ANA titers after the start of biologics. No previous study has comprehensively investigated change in ANA titers over time in individual patients or the effectiveness of certolizumab pegol or tildrakizumab. Objectives: This study evaluated change in ANA titers in individual patients during treatment with biologics, including certolizumab pegol and tildrakizumab. Methods: 111 patients were included in this study. Change in ANA was regarded as significant when the ANA titer was ×80 or more in patients with a previously undetectable ANA titer or when it increased by fourfold or more in those with a detectable ANA titer before treatment. Results: The ratios of patients with a significant change in ANA titer who were treated with a tumor necrosis factor (TNF) inhibitor, interleukin (IL)-17 inhibitor, or IL-23 inhibitor were 34.9% (15/43), 0.0% (0/32), and 0.0% (0/36), respectively. There were 4 patterns of significant change in ANA titer: (i) an increase (n=8), (ii) a decrease after an increase (n=4), (iii) a decrease after an increase with a drug change (n=2), and (iv) an increase after a decrease after an increase (n=1). No symptom suggesting lupus syndrome was noted. Conclusions: ANA titers must be carefully monitored throughout treatment with biologics, especially TNF inhibitors, and the possibility of lupus-like syndrome should be excluded. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Objective: The effect of severe acute respiratory syndrome-coronavirus-2 (SARS‑CoV‑2) infection on autoimmunity in both disease and post-disease stages has not been fully explained. There is not enough information about the evaluation of autoimmune antibodies in convalescent SARS-CoV-2 patients. This study aimed to investigate the presence and types of autoantibodies in post-illness coronavirus disease-2019 (COVID-19) patients and to compare them with indirect immunofluorescence assay (IIF)-antinuclear antibody (ANA) results before SARS-CoV-2 infection. Materials and Methods: Twenty-four COVID-19 patients with known and reported ANA test results prior to SARS-CoV-2 infection were included in this study. Patients’ IIF-ANA, extractable nuclear antigen blot and anti-dsDNA tests were studied three and nine months after SARS-CoV-2 infection. Results: Three months after SARS-CoV-2 infection, 41.66% of patients had a positive IIF-ANA test. When we compared these results with pre-infection ANA results, 3 patients (12.5%) were variable. The first case was chromosomal granular positive before infection and was found to be homogeneous, and cytoplasm was speckled positive after infection. Additionally, Scl-70, DFS70, and anti-dsDNA were found to be positive. We think that lupus symptoms were triggered after COVID-19. The second case had negative ANA before infection, while the ANA was antinuclear membrane positive (2+) three months after infection. Also, anti-RNP/Sm was detected as positive. The third case had negative ANA before infection, and was detected to have speckled weakly positive ANA three months after infection. However, autoantibody positivity was not detected. Conclusion: As a result, these data support the idea that SARS-CoV-2 infection may trigger autoimmunity and be associated with the development of autoantibodies. [ABSTRACT FROM AUTHOR]

Neonatal lupus erythematosus (NLE) is a congenital autoimmune condition in which the transplacental passage of immunoglobulin G (IgG) directed against auto-antigens causes clinical symptoms in the foetus or neonate. Anti-Ro/SS-A, anti-La/SS-B, and to a lesser extent, anti-U1RNP autoantibodies (aAbs) have the strongest association with NLE. However, ~ 50% of affected mothers are asymptomatic despite carrying those aAbs. The clinical picture of the disease is very diverse. Cardiac manifestations are the most severe, including congenital heart block (CHB), with a mortality rate of ~18%. Preventative therapy with hydroxychloroquine (HCQ) reduces the recurrence rate of CHB in subsequent pregnancies by ~50%. [ABSTRACT FROM AUTHOR]

We described nailfold videocapillaroscopy (NVC) findings and estimated the prevalence of serum anti-nuclear (ANA) and extractable nuclear antigen autoantibodies (ENA) in a cohort of sarcoidosis patients, comparing them with adequate healthy controls (HCs) and with primary Raynaud's phenomenon patients (PRPs). NVC findings were also correlated with the occurrence of autoantibodies, current treatment, laboratory parameters, variables of lung function and whole-body imaging data. Twenty-six patients with sarcoidosis were assessed through NVC, laboratory parameters, pulmonary function tests, chest-X ray and 18- fluorodeoxyglucose positron emission tomography/computed tomography. The NVC parameters and ANA/ENA dosage were recorded also in 30 PRPs and 30 HCs. Sarcoidosis patients showed a higher rate of capillary dilations and nonspecific abnormalities and a lower mean capillary absolute number than PRPs and HCs (p < 0.01 for all comparisons). The prevalence of ANA positivity was higher in patients with sarcoidosis compared with PRPs and HCs (p < 0.02 for both), whereas ENA positivity was detected in one sarcoidosis patient (Ro52). Among sarcoidosis patients, the mean capillary absolute number negatively correlated with the C-reactive protein concentrations and was positively associated with the forced vital capacity percentage. Instead, a negative correlation was detected between serum ACE levels and the presence of capillary dilations (all p < 0.05). Our findings suggest a microvascular involvement in sarcoidosis whose investigation by NVC might be useful for the follow-up of patients displaying RP. Autoantibody positivity in sarcoidosis might suggest autoimmune implications in the disease or the production of autoantibodies reactive to tissue damage. [ABSTRACT FROM AUTHOR]

Objective To investigate the combination of recombinant human thrombopoietin ( rhTPO) combined with high-dose short-cycle dexamethasone ( hexadecadrol, HDD) regimen in the treatment of antinuclear antibody (ANA) positive adults with immune thrombocytopenia (immune thrombocytopenia, ITP) efficacy and safety. Methods A total of 66 adult patients with ANA-positive immune thrombocytopenia diagnosed in Qujing First People's Hospital from August 2020 to December 2021 were selected and divided into HDD alone group (n = 22), rhTPO alone group (n = 22) and combination group (n = 22) by random number table method. The HDD alone group was treated with high-dose short-cycle dexamethasone (HDD), the rhTPO alone group was treated with rhTPO, and the combination group was treated with HDD and rhTPO. The liver and kidney-related indexes, platelet count, clinical efficacy including total effective rate, recurrence rate, time to effective standard of platelet count and adverse reactions were compared between the three groups before and after treatment. Results The total effective rate of the combination group was significantly higher than that of HDD alone group and rhTPO alone group (P < 0.05). The platelet count of combination group was higher than that of HDD alone group and rhTPO alone group, and the effective time of platelet count was shorter than that of HDD alone group and rhTPO alone group (P < 0.05). There was no significant difference in platelet transfusion rate among the three groups (P > 0.05). There was no significant difference in the incidence of total adverse reactions among the three groups (P > 0.05). There were no significant differences in ALT, AST, BUM and Scr levels among the three groups before and after treatment (P > 0.05). Compared with before treatment, there were no significant differences in ALT, AST, BUM and Scr levels among the three groups after treatment (P > 0.05). After the course of treatment, there was no significant difference in the recurrence rate among the three groups (P > 0.05). Conclusion The use of rhTPO combined with high-dose short-cycle HDD therapy can significantly improve the clinical efficacy of ANA-positive adult ITP, increase the number of platelets, and has good safety. [ABSTRACT FROM AUTHOR]

Carmen Bobeica,1,&ast; Elena Niculet,1,2 Carmina Liana Musat,1 Mihaela Craescu,1,&ast; Bogdan Ioan Stefanescu,3,&ast; Ciprian Dinu,4,&ast; Iulia Chiscop,3,&ast; Silvia Chirobocea,5,&ast; Luiza Nechita,6,&ast; Alina Viorica Iancu,1,&ast; Victorita Stefanescu,7,&ast; Gabriela Balan,6,8,9,&ast; Ioana Anca Stefanopol,1,10,&ast; Ana Maria Pelin,11,&ast; Alin Laurentiu Tatu2,6,12 1Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dun&abreve;rea de Jos” University of Galați, Galati, 800008, Romania; 2Multidisciplinary Integrated Center of Dermatological Interface Research MIC-DIR (Centrul Integrat Multidisciplinar de Cercetare de Interfata Dermatologica - CIM-CID), “Dun&abreve;rea de Jos” University, Galați, 800008, Romania; 3Clinical Surgical Department, Faculty of Medicine and Pharmacy, “Dun&abreve;rea de Jos” University, Galați, Romania; 4Dental Department, Faculty of Medicine and Pharmacy, Dun&abreve;rea de Jos University, Galați, Romania; 5Department of Neurology, Municipal Emergency Hospital, Moinești, Romania; 6Clinical Medical Department, Faculty of Medicine and Pharmacy, Dun&abreve;rea de Jos University, Galați, Romania; 7Medical Department, Faculty of Medicine and Pharmacy, Dun&abreve;rea de Jos University, Galați, Romania; 8Department of Gastroenterology, “Sf. Apostol Andrei” County Emergency Clinical Hospital, Galați, Romania; 9Research Center in the Field of Medical and Pharmaceutical Sciences, “Dun&abreve;rea de Jos” University, Galați, Romania; 10Department of Pediatrics, Clinical Emergency Hospital for Children “Sf. Ioan”, Galati, Romania; 11Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, “Dun&abreve;rea de Jos” University, Galați, Romania; 12Dermatology Department, “Sf. Cuvioasa Parascheva” Clinical Hospital of Infectious Diseases, Galați, Romania&ast;These authors contributed equally to this workCorrespondence: Elena Niculet; Carmina Liana Musat, Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, “Dun&abreve;rea de Jos” University of Galați, 35 Alexandru Ioan Cuza Street, Galați, 800008, Romania, Tel +40741398895 ; +40723338438, Email helena_badiu@yahoo.com; carmina.musat@ugal.roAbstract: Systemic sclerosis (SSc) is a chronic inflammatory disease with an autoimmune substrate that affects the skin and a large number of internal organs. The chronic inflammatory process is sustained by a wide range of cytokines and chemokines, which are discharged by inflammatory cells, with fibrosis and nail bed vascular changes (disorganized vasculature architecture with microhemorrhages, megacapillaries and areas without capillaries). Confocal microscopy contributes to the understanding of the molecular mechanism involved in chronic inflammation and mainly targets the field of research. Coherent optical tomography, capillaroscopy, and skin biopsy are useful for the differential diagnosis of SSc with other sclerodermoid syndromes. The immunological profile is a classification criterion for SSc and directs the diagnosis to the two subsets of the disease. Multisystemic damage requires evaluation with the help of a set of investigations specific to each affected organ, such as: diffusing capacity for carbon monoxide, forced vital capacity, 6-minute walk test, high-resolution computed tomography standard and reduced sequential, cardiac ultrasound and right cardiac catheterization. The current possibilities of diagnosis, treatment and monitoring are permanently adapting to new medical discoveries.Keywords: systemic sclerosis, antinuclear antibodies, capillaroscopy, confocal microscopy, coherent optical tomography

Objective: Eltrombopag remains a prominent option in the treatment of steroid-dependent or steroid-refractory immune thrombocytopenia (ITP) patients. Unfortunately, not all patients respond to eltrombopag. Antinuclear antibody (ANA) positivity can be seen at rates of up to 30% in ITP patients. Despite being widely used, more markers to predict the response to eltrombopag are still needed. In the present study, we aimed to show the association between ANA positivity and eltrombopag response in ITP patients. Materials and Methods: Patients who were diagnosed with ITP in the Trakya University Faculty of Medicine's Department of Hematology and who underwent eltrombopag treatment due to their resistance to steroids and other treatments were included in our study. ANA measurement was performed by indirect fluorescent antibody method and titers of 1: 160 and above were considered positive. ANA measurements were made before starting eltrombopag. Results: Forty-five patients were included in our study, 33 being women and 12 men. The mean age of the patients was 45.73 years. There were 14 patients with ANA positivity and 31 patients were found to be ANA-negative. Response rates were higher in ANA-negative patients compared to ANA-positive patients in the 1st and 6th months of eltrombopag treatment (p

The I nternational C onsensus on A NA P atterns (ICAP) is an ongoing international initiative dedicated to harmonizing technical and interpretation aspects of the HEp-2 IFA test. Comprised of internationally recognized experts in autoimmunity and HEp-2 IFA testing, ICAP has operated for the last 10 years by promoting accurate reading, interpretation, and reporting of HEp-2 IFA images by professionals involved in various areas related to autoimmune diseases, such as clinical diagnostic laboratories, academic research, IVD industry, and patient care. ICAP operates through continuous information exchange with the international community and encourages the participation of younger experts from all over the world. The 7th ICAP workshop has addressed several aspects that originated from this interaction with the international community and has effectively established objective goals and tasks to be delivered over the next two years. Some of these are outlined in this article, including the planning of three audio-visual educational modules to be posted at the www.anapattern.org website, the classification of two novel HEp-2 IFA patterns, the implementation of a project dedicated to continuously updating the information on the clinical and immunologic relevance of the HEp-2 IFA patterns, and the launch of two additional branches of the HEp-2 Clinical and Immunological (HEp-2 CIC) project. • ICAP promotes harmonization in performance, interpretation, and reporting HEp-2 IFA. • The AC-2, but not the novel AC-30 pattern, is associated with anti-DFS70 antibodies. • The novel AC-31 nuclear pattern is strongly associated with anti-Ro60 antibodies. • Competent/Expert definition depends on analyst expertise and the image under analysis. [ABSTRACT FROM AUTHOR]

Immunity play a pivotal role in the risk of ischemic stroke, and studies have also shown a relationship between ischemic stroke and autoimmune diseases. In light of this we conducted a prospective cohort study to elucidate the impact of antiphospholipid antibodies (aPLs), antinuclear antibodies (ANA), and anti-extractable nuclear antigen autoantibodies (anti-ENA) on the prognosis of ischemic stroke. 245 stroke patients were recruited in this single-center study and followed up with for 3 years. Autoantibodies, including aPLs (ACA, anti-β2GPI, LA), ANA and anti-ENA were evaluated in recurrent ischemic stroke (RIS) and nonrecurrent ischemic stroke (nonRIS). Stroke severity was judged using the National Institutes of Health Stroke Scale (NIHSS). For preventive treatment, 42 IS patients with positive aPLs + ANA/anti-ENA were randomized 1:1 into a hydroxychloroquine (HCQ) treatment group and a control group, and the prognoses were compared. The positive rate of ACA IgG (p = 0.018), anti-β2GPI IgG (p = 0.047), LA (p = 0.023), and aPLs + ANA/anti-ENA (p = 0.000) were significantly higher in patients with RIS compared to patients with nonRIS, and aPLs + ANA/anti-ENA (HR2.31, 95 % CI1.02-5.25, p = 0.046) and hypertension (HR2.50, 95 % CI1.17-5.35, p = 0.018) were the independent risk factors of recurrence. There were differences in NIHSS at month 36 between those positive and negative for aPLs + ANA/anti-ENA (p = 0.001, Eta2 = 0.052), anti-ENA (p = 0.016, Eta2 = 0.030), ANA (p = 0.035, Eta2 = 0.022), and LA (p = 0.016, Eta2 = 0.028). Furthermore, the recurrence rate of the HCQ treatment group was lower than that of the control group (p = 0.024). Co-positivity of aPLs and ANA/anti-ENA is an independent risk factor for RIS. However, HCQ therapy may reduce the recurrence rate of IS for these patients. [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.

Antinuclear antibody (ANA) testing is common practice among health care practitioners when evaluating children and adolescents with non-specific symptoms including fatigue and aches and pains. When positive, ANA results often lead to referrals to pediatric rheumatologists as these antibodies may be key indicators for specific pediatric rheumatologic diagnoses. The reliability and reproducibility of ANA tests varies with assay techniques and validation and interpretation of results. In the following article, review of ANA testing in pediatrics is provided along with case examples that demonstrate the reliability and reproducibility of these results in specific scenarios common in the practice of pediatric rheumatology. Guidelines for more accurate utilization of ANA testing are presented with the aim to improve testing and interpretation by ordering clinicians.

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. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome (SjS) is a heterogeneous systemic disease. The abnormal responses to La/SSB and Ro/SSA of both B-cells and T-cells are implicated as well as others, in the destruction of the epithelium of the exocrine glands, whose tissue characteristically shows a peri-epithelial lymphocytic infiltration that can vary from sicca syndrome to systemic disease and lymphoma. Despite the appearance of new autoantibodies, anti-Ro/SSA is still the only autoantibody included in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria and is used extensively as a traditional biomarker in clinical practice. The study and findings of new autoantibodies in SjS has risen in the previous decade, with a central role given to diagnosis and elucidating new aspects of SjS physiopathology, while raising the opportunity to establish clinical phenotypes with the goal of predicting long-term complications. In this paper, we critically review the classic and the novel autoantibodies in SjS, analyzing the methods employed for detection, the pathogenic role and the wide spectrum of clinical phenotypes. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to evaluate ANA (Anti-Nuclear Antibodies) in healthy first degree and second-degree relatives of patients with connective tissue diseases. Methodology: This was a Case Control study conducted in medical wards of Dr D.Y. Patil Medical College and hospital, Pimpri, Pune. This was carried out from October 2020 to September 2022 among Healthy first degree and second-degree relatives (on the basis of history and routine investigations), aged > 18 & <50, of patients with connective tissue diseases. Results: We found that nearly 44% and 28% of the study population had family history of Rheumatoid Arthritis (RA) and Systemic lupus Erythematosus (SLE) respectively. It was found from our study that the severity of disease differs almost identically between cases and controls, with disease being more common in both groups for first degree relatives. The difference in Ana Positivity between cases and controls was statistically significant. (p value <0.05). Conclusion: Relatives of connective tissue disorder patients of autoimmune tend to be at higher risk for developing autoimmune disorders, although it is difficult to assess the risk in each individual family member. [ABSTRACT FROM AUTHOR]

Autoantibodies can be detected in blood and are a sign of autoimmunity. They may help predict the risk of immunotherapy induced adverse event (iRAE). We tested this hypothesis in a retrospective series of 68 patients treated with pembrolizumab for metastatic bladder cancer. Our results show that the presence anti-nuclear antibodies > 1/160 is associated with iRAE and limiting toxicity of pembrolizumab. Introduction: Immune checkpoint inhibitor are standard therapy in metastatic urothelial carcinoma. No predictive biomarker of immune related adverse events (iRAE) exists. Antinuclear antibodies (ANA) can be the sign of a subclinical autoimmune condition that could be enhanced by Immune checkpoint inhibitor. We decided to assess the predictive value of baseline autoantibodies and ANA for iRAE in metastatic urothelial carcinoma patients treated with pembrolizumab and explore their prognostic signification. Patients and Method: Data concerning patients treated in our institution between 2015 and 2020 with pembrolizumab for metastatic urothelial carcinoma with available baseline value of ANA and other autoantibodies was collected. ANA with titer > 1/80 were defined positive. Results: A total of 68 patients were included. Fifty-five (80%) had ANA > 1/80 and among them 21 patients (30%) had ANA > 1/160. Seven patients with ANA > 160 (33%) presented iRAE vs. 5 patients (10%) in the rest of the population. Presence of ANA > 160 was significantly associated with iRAE (P = .029) and limiting toxicity (P = .048) in univariate analysis. iRAE tend to occur earlier, before the third cycle, for patients with ANA > 1/160 as compared to rest of the patients (28% vs. 6%, P = .052). Exploratory analysis did not reveal correlation between progression free survival or overall survival and ANA > 1/160 in univariate or in multivariate analysis including the Bellmunt score (HR = 0.7, 95%CI [0.38-1.35], P = .5). Conclusion: The presence of ANA > 1/160 is associated with iRAE and limiting toxicity of pembrolizumab. [ABSTRACT FROM AUTHOR]

Nucleolar staining is one of the standard patterns in immunofluorescence antinuclear antibodies (ANA), seen in 5–9% of ANA in various conditions. Antinucleolar antibodies (ANoA) are classified into 3 patterns in the International Consensus on ANA Patterns (ICAP) classification; AC-8 homogeneous pattern, AC-9 clumpy pattern, and AC-10 punctate pattern. Specificities known to show AC-8 include anti-Th/To, -PM-Scl, -nucleophosmin/B23, -nucleolin/C23, -No55, and others. AC-9 is seen by anti-fibrillarin/U3RNP and AC-10 by anti-RNA polymerase I and hUBF/NOR-90. ANoA has been classically known to be associated with scleroderma (SSc) and the characterization of nucleolar antigens identified several autoantigens recognized by SSc autoantibodies. The clinical association of anti-Th/To, PM-Scl, fibrillarin/U3RNP, and RNA polymerase I with SSc or SSc-overlap syndrome is well established, and commercial assays are developed. Anti-hUBF/NOR90, nucleophosmin/B23, and nucleolin/C23 are known for decades and reported in systemic autoimmune rheumatic diseases (SARDs), malignancies, graft versus host disease (GVHD), and others; however, their clinical significance remains to be established. [ABSTRACT FROM AUTHOR]

Dermatomyositis is a chronic inflammatory disease involving the skin and muscles. It most commonly occurs in adults with preponderance in females, but pediatric occurrence is also possible. The risk of malignancy in adult patients with dermatomyositis was reported to be 4.66-fold higher compared to that in the general population. A significantly increased risk of malignancy was reported within the first 12 months following the diagnosis of dermatomyositis (standardized incidence ratio equaled 17). One of the characteristic laboratory findings associated with dermatomyositis is the presence of circulating autoantibodies which are classified into two subgroups: myositis-specific and myositis-associated autoantibodies. It was shown that specific types of antibodies might be associated with an increased risk of malignancy. Current literature data indicate that the strongest correlation with malignant diseases was reported in anti-TIF1-γ-positive patients who were at a 9.37-fold higher risk of cancer. A 3.68-fold increase in the risk of cancer was also reported among patients with anti-NXP2 antibodies. Malignant diseases were reported in 14–57% of patients with anti-SAE antibodies. The presence of other autoantibodies may also be associated with an increased risk of malignancy. These data indicate that patients with circulating anti-TIF1-γ, anti-NXP2, and anti-SAE should be very closely monitored for dermatomyositis-associated malignant comorbidities. The aim of this review is to summarize the current data regarding the link between malignancy and the presence of specific antibodies in patients with dermatomyositis. [ABSTRACT FROM AUTHOR]

Anti-fibrillarin autoantibodies are useful for the diagnosis and prognosis of systemic sclerosis (SSc). Anti-fibrillarin produces a clumpy nucleolar pattern in indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA). Here we develop and validate a reliable cell-based anti-fibrillarin assay (Fibrillarin/CBA) for use in clinical diagnostic laboratories. A TransMembrane Signal was fused to the human fibrillarin gene (TMS-fibrillarin). HEp-2 cells overexpressing transgenic TMSfibrillarin at the cytoplasmic membrane were used as IFA substrate in the Fibrillarin/CBA. Sixty-two serum samples with nucleolar pattern in the HEp-2 IFA (41 clumpy; 21 homogeneous/punctate) were tested for anti-fibrillarin using Fibrillarin/CBA, immunoprecipitation (IP), line-blot and ELISA. In addition, samples from 106 SSc-patients were evaluated with Fibrillarin/CBA and the results were correlated with disease phenotypes. Thirty-eight of 41 samples with the clumpy nucleolar pattern (92.7%) were positive in the Fibrillarin/CBA, while all 21 samples with other nucleolar patterns were negative. Fibrillarin/CBA results agreed 100% with IP results. Among the 38 Fibrillarin/CBA-positive samples, only 15 (39.5%) and 11 (29%) were positive for anti-fibrillarin in line-blot and ELISA, respectively. Higher frequency of diffuse cutaneous SSc (dcSSc) phenotype (72.7% vs 36.8%; p=0.022), cardiac involvement (36.4% vs 6.5%; p=0.001) and scleroderma renal crisis (18.2% vs 3.3% p = 0.028) was observed in SSc patients with positive compared to negative Fibrillarin/CBA result. Performance of Fibrillarin/CBA in the detection of anti-fibrillarin autoantibodies was comparable to the gold standard IP. Positive Fibrillarin/CBA results correlated with disease phenotypes known to be associated with anti-fibrillarin autoantibodies, underscoring the clinical validation of this novel assay. [ABSTRACT FROM AUTHOR]

Background: Between 1988 and 2012, prevalence of antinuclear antibodies (ANA) increased in the U.S., especially in adolescents and non-Hispanic Whites. Female predominance of ANA suggests a role for hormonal factors, including xenobiotic exposures that may disrupt endocrine signaling. Benzophenone-3 (BP-3) is one such chemical with increasing exposure through sunscreen use. We investigated whether urinary BP-3 levels were related to ANA in adolescents and young adults. Methods: In a sample of 1,785 individuals ages 12-39 years in the National Health and Nutrition Examination Survey (NHANES; 2003-4, 2011-12), we examined cross-sectional associations of ANA (N=192; 3+ or 4+ at the 1:80 dilution, measured by HEp-2 immunofluorescence) with urinary BP-3, and other phenols bisphenol-A, triclosan, and parabens. Adjusted prevalence odds ratios (POR) were calculated in season-stratified models [winter (November-April) and summer (May-October)], given differences in sunscreen use and BP-3 concentrations. Results: BP-3 concentrations (detected in >98.5% of individuals) did not differ by ANA positivity in the summer (geometric mean, GM 30.6 ng/ml ANApositive vs. 35.3 ANA-negative; GM ratio 1.15), but in winter were higher among ANA-positives (50.2 vs. 20.1 ANA-negative; GM ratio 2.50). ANA was associated with log10BP-3 in winter (POR 1.57; 95%CI 1.07-2.30 per unit increase) but not summer (0.94; 0.61, 1.44; interaction p=0.09). Triclosan, parabens, and bisphenol-A levels were unrelated to ANA overall or by season (ORs 0.64 to 1.33). Conclusions: The association of urinary BP-3 with ANA in the winter may reflect different exposure patterns or unmeasured confounders. Findings warrant replication in prospective studies and including past and year-round exposures. [ABSTRACT FROM AUTHOR]

Objective This study analysed the very early disease of SSc (VEDOSS) characteristics in a group of 217 patients with RP and at least one manifestation of SSc in search of predictors for the progression to SSc. Methods This was a cross-sectional single-centre analysis of patients presenting with RP with a specific SSc clinical manifestation or SSc autoantibody or SD pattern at nailfold capillaroscopy (SD-NFC), without skin involvement, who attended a scleroderma outpatient clinic between 2010 and 2019. The performance of VEDOSS and the importance of the combination of VEDOSS characteristics to predict the progression to SSc were evaluated. Results Among 217 patients, 153 (70.5%) were classified as SSc, including 65 (30%) in the first investigation; 69.3% of the SSc patients met VEDOSS criteria compared with 6.3% of patients who did not progress to SSc. The combinations most associated with progression to SSc were RP + puffy fingers (PF) + positive ANA + SD-NFC and/or SSc-specific antibody (VEDOSS level 2), with an odds ratio (OR) of 19.52 (95% CI 4.48, 85.06; P  < 0.001) and RP + PF + positive ANA (VEDOSS level 1; 'red flags') (OR 15.45; P  < 0.001), while combinations without non-RP clinical symptoms, as RP + SD-NFC (OR 0.03; P  < 0.001) and RP + anticentromere + SD-NFC (OR 0.06; P  = 0.006) were associated with non-progression to SSc. Conclusion Among patients with RP with at least one manifestation of SSc, without skin involvement, combinations of VEDOSS characteristics were the strongest predictors of progression to SSc at a median follow-up of 4 years. [ABSTRACT FROM AUTHOR]

Background: The presence of Antinuclear antibodies/Dense Fine Speckled 70 (ANA/DFS70) has been proposed as a negative biomarker in the process of exclusion of systemic autoimmune/autoinflammatory rheumatic diseases (SARD). The purpose was to evaluate and characterize ANA/DFS70 patients in a large Colombian population with SARD; rheumatoid arthritis (RA), Psoriasis (PsO), Undifferentiated connective tissue disease (UCTD), first-degree relatives of (FDR), and healthy controls (HC). Methods: ANA determination was performed using indirect immunofluorescence. Samples with positive dense fine granular staining in the nucleoplasm of the interphase cell (AC2) fluorescence were confirmed with CytoBead/ANA and ANA/modified (Knocked out for the PSPI1 gen). Results: 530 mestizo Colombian participants were included. ANA/DFS70 antibody positivity in the whole group was 2.3%, and 0.8% in SARD; no RA patients were positive. ANA/DFS70 positives in UCTD were three women; the average time of evolution of the disease was 9.4 years. The most frequent clinical findings were arthralgias, non-erosive arthritis, and Raynaud's phenomenon. The PsO positive was a woman with C-reactive protein (CRP) positivity and a negative erythrocyte sedimentation rate (ESR) without any other positive autoantibody or extracutaneous manifestation. FDR and HC positives were 7/8 women. All were negative for other autoantibodies. Conclusions: ANA/DFS70 autoantibodies were present in Colombian patients with SARD at a shallow frequency, they were more prevalent in healthy individuals. [ABSTRACT FROM AUTHOR]

Antinuclear antibodies (ANAs) are a serological hallmark of systemic autoimmune rheumatic diseases (SARDs); however, few studies have investigated their post-treatment levels. The mechanism by which ANA titers are upregulated in SARDs remains unclear. We assessed factors associated with the ANA titer after treatment. In this retrospective study, we analyzed the clinical database of Zhongshan Hospital, Medical College of Xiamen. Demographic data and baseline and 12-month post-treatment ANA titers were collected. Bivariate and multivariate analyses were performed to determine the factors associated with the ANA titer. This study identified 31,923 patients who underwent ANA assay for SARDs screening, and a total of 1043 patients were included in the study. Approximately 16% of the patients showed a decrease in the serological ANA titer. Younger patients (< 20) were 3 × more likely to experience such a decrease (P = 0.005) compared to older patients (≥ 60 years). Having a baseline ANA titer > 1:10,000 was associated with an increase likelihood of a decrease in the serological ANA titer compared with baseline ANA titer 1:10,000, 1:3200 and 1:1000 (P < 0.001). We found that a decrease in the serum ANA titer at 12 months after treatment for SARDs is associated with age and ANA baseline titers. [ABSTRACT FROM AUTHOR]

Background: Several autoimmune features occur during coronavirus disease 2019 (COVID‐19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID‐19. Methods: We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome‐wide serological profiling in a multicentric cohort of 175 COVID‐19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls. Results: Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID‐19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID‐19. Furthermore, patients with severe COVID‐19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS‐CoV‐2‐specific antibody titers in COVID‐19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen‐specific humoral responses. Notably, the qualitative breadth of antibodies cross‐reactive with other coronaviruses was comparable in ANA‐positive and ANA‐negative individuals during acute COVID‐19. In autoantibody‐positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID‐19 and alterations of the B‐cell compartment after recovery. Conclusion: Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS‐CoV‐2 infection, while the presence of autoantibodies in COVID‐19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures. [ABSTRACT FROM AUTHOR]

(1) Background: Autoimmune diseases are characterized by autoantibodies directed to a large number of antigenic targets and are measured using serum as sample matrix. Although serum is a very common specimen type, it comes with certain drawbacks. Most importantly, it depends on venous puncture and requires medical personnel for sampling. This is of particular importance in light of the limited healthcare access of patients with autoimmune diseases during the COVID-19 pandemic. Consequently, alternative sample matrices are being explored for the measurement of autoantibodies. Our study aimed to establish the feasibility of measuring autoantibodies in saliva samples using a novel and highly sensitive method for the detection of autoantibodies. (2) Methods: A total of 48 serum/saliva pairs were collected and tested using a novel particle-based multi-analyte technology (PMAT) system for the presence of a wide range of autoantibodies. (3) Results: A high level of correlation was observed between the results obtained with serum and saliva (Spearman's rho = 0.725). Study participants clearly preferred saliva over serum sampling as part of the usability assessment. (4) Conclusions: Saliva represents a promising alternative sample matrix for the detection of autoantibodies. The usability study showed a clear preference of saliva over serum as a sample matrix. [ABSTRACT FROM AUTHOR]