Search Results (156)

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings. Full article

Background: Antinuclear antibodies (ANAs) serve as crucial biomarkers for diagnosing systemic autoimmune diseases; however, their interpretation can be complex and may not always correlate with clinical symptoms. Methods: A comprehensive narrative review was conducted to evaluate the peer-reviewed literature published between 1961 and 2025. Databases, including PubMed and Scopus, were searched using combinations of controlled vocabulary and free-text terms relating to antinuclear antibodies and their clinical significance. The objective was to gather and synthesize information regarding the diagnostic utility and interpretation of ANA testing in routine medical practice. Discussion: The indirect immunofluorescence assay (IIF) on HEp-2 cells is established as the gold standard for detecting ANAs, facilitating the classification of various fluorescent patterns. While a positive ANA test can suggest autoimmune disorders, the presence and titre must be interpreted alongside clinical findings, as low titres often lack diagnostic significance. Findings indicate that titres higher than 1:160 may provide greater specificity in differentiating true positives from false positives in healthy individuals. The study also emphasizes the relevance of fluorescence patterns, with specific patterns linked to particular diseases, although many do not have strong clinical correlations. Moreover, certain autoantibodies demonstrate high specificity for diseases like systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Ultimately, while ANA testing is invaluable for diagnosing connective tissue diseases, healthcare providers must consider its limitations to avoid misdiagnosis and unnecessary treatment. Conclusions: ANA testing is a valuable tool in the diagnosis of connective tissue diseases, but its interpretation must be approached with caution. Clinical context remains crucial when evaluating ANA results to avoid misdiagnosis and overtreatment. This review is about the diagnostic aspects and clinical consequences of ANA testing, as well as highlighting both the diagnostic benefits and the potential limitations of this procedure in everyday clinical practice. The review fills a gap in the literature by integrating the diagnostic and clinical aspects of ANA testing, with a focus on real-world interpretation challenges. Full article

Background: Antiphospholipid syndrome (APS) is one of the highest risk factors for obstetric complications. This article contains a case report of a patient with obstetric APS who experienced fetal loss during their first pregnancy and experienced a successful second pregnancy upon treatment with acetylsalicylic acid (ASA), low-molecular-weight heparin (LMWH), and hydroxychloroquine (HCQ). We compare placental pathology in these two pregnancies and discuss the impact of antiphospholipid antibodies and clinical management on pregnancy outcomes. We also propose methods to monitor obstetric antiphospholipid syndrome (OAPS) patients during pregnancy. Methods: A 26-year-old woman presented with a history of stillbirth at 25 weeks of pregnancy due to placental insufficiency. Before pregnancy, she experienced symptoms suggestive of autoimmune disease (thrombocytopenia, recurrent mouth aphthous ulcers, and Raynaud’s phenomenon) but had no diagnosis. Placental dysfunction correlated with the high ratio of sFlt-1/PIGF (soluble fms-like tyrosine kinase 1 and the placental growth factors index). Laboratory tests revealed the presence of antinuclear antibodies (ANAs) and triple positivity for antiphospholipid antibodies (aPLs). Results: Following the initiation of treatment for OAPS and regular monitoring consistent with current guidelines, the patient conceived and successfully delivered a healthy child. Conclusions: Adequate therapy and close monitoring during pregnancy, including clinical observation, placental biomarkers and regular ultrasonography, may help to reduce the risks and increase chances for optimal pregnancy outcomes. Additionally, pathological examination and clinical collaboration are essential components in future pregnancy counseling and should be a part of multidisciplinary management. Full article

Background: Autoimmune liver diseases (ALDs) are a diverse group of chronic inflammatory disorders. Individuals with a history of one autoimmune disease (AD) are at a substantially increased risk of developing additional autoimmune conditions. Polyautoimmunity has increasingly been recognized as a factor associated with a more complex disease course and poorer long-term outcomes. Methods: This retrospective, cross-sectional observational study reviewed medical records of patients diagnosed with ALDs who had been admitted to the gastroenterology clinic. Results: A total of 457 patients with ALDs were included. Polyautoimmunity was present in 194 patients (42.5%), and multiple autoimmune syndrome (MAS) was diagnosed in 26 of these patients (5.7%). Serological comparisons revealed that antinuclear antibody (ANA) positivity was significantly more common in the polyautoimmunity group. Only 22.2% of the patients with polyautoimmunity were ANA-negative, compared with 52.9% in those without. An ROC curve analysis was conducted to assess the predictive value of clinical and laboratory variables for polyautoimmunity. Among all the tested parameters, ANA positivity (>+2) had the strongest predictive value (AUC: 0.724). A disease duration longer than 6.5 years followed, with a moderate discriminative capacity (AUC: 0.677). Additionally, lower albumin levels (<3.0 g/dL) and elevated erythrocyte sedimentation rates (ESRs) (>29.5 mm/h) were significantly associated with polyautoimmunity. Conclusions: In our cohort, 42.5% of patients had at least one additional autoimmune disorder, highlighting the need for a systemic and comprehensive approach to patient care. Simple and accessible markers—such as ANA titers, disease duration, albumin levels, and ESRs—may help to identify patients at greater risk. Full article

Sjogren’s syndrome is an autoimmune disease that may be triggered by environmental factors. While the impact of perfluoroalkyl substances (PFASs) on the human immune system has been investigated, their specific effect on Sjogren’s syndrome remains unreported. We conducted this study to evaluate the association between PFAS exposure and clinical manifestations of pSS. In total, 136 patients with pSS and 148 healthy controls in the Second Affiliated Hospital of Zhejiang University School of Medicine were investigated. The concentrations of perfluoroundecanoic acid (PFUdA) in the pSS group were statistically significantly higher than those in the healthy control group. Compared to patients without leukopenia and thrombocytopenia, those with the condition had significantly lower concentrations of perfluorononanoic acid (PFNA). The serum levels of PFNA and perfluorodecanoic acid (PFDA) were found to be lower in patients with a high antinuclear antibody (ANA) titer compared to those with a low ANA titer. The serum levels of PFNA were found to be lower in patients who were anti-Sjögren’s syndrome A (anti-SSA)-positive compared to those who were anti-SSA-negative. These results indicate that the levels of serum PFASs may be correlated with the disease activity in pSS patients, and there might be an association between PFASs and the onset of pSS. Full article

Drug-induced autoimmune hepatitis (DIAIH) is a relatively new subtype of idiosyncratic drug-induced liver injury (iDILI), but the features of DIAIH have been variably described due to the inhomogeneity of assessed study cohorts. The aim of this analysis is to harmonize DIAIH cohorts by unifying causality assessments, which may help characterize the features of DIAIH. Methods: Published reports of DIAIH cases were evaluated for the causality assessment methods used to verify the diagnosis of DIAIH. This disorder consists of two parts, i.e., the iDILI part and the autoimmune (AIH) part, whereby each part needs a specific diagnostic algorithm. The validated and scoring Roussel Uclaf Causality Assessment (RUCAM) is privileged for assessing the iDILI part, and the validated, simplified AIH score is the perfect choice for evaluating the AIH part. The analysis of DIAIH publications revealed that 12/20 reports (60%) presented cases assessed by both the RUCAM and the simplified AIH score, providing 49 drugs and drug combinations as causative drugs in up to 25 cases of DIAIH. Serum alanine aminotransferase activities of up to 3489 UL and high titers of autoimmune parameters such as anti-nuclear antibodies, anti-smooth-muscle antibodies, and soluble liver antigen antibodies supported DIAIH diagnosis. In contrast, 4/20 reports (20%) applied only RUCAM, and 2/20 reports (10%) used only the simplified AIH score; these 6 reports therefore provided insufficient criteria for a valid DIAIH diagnosis. Moreover, 2/20 reports (10%) did not use any causality algorithm, providing elusive features of DIAIH. While DIAIH is clearly restricted to drugs as responsible agents, this term is erroneously used to refer to disease induced by non-drugs such as herbs, green tea, dimethoate (an organophosphate insecticide), dietary supplements, biologics, herbal remedies, different viruses, and bacteria, as well as vaccines. For diseases induced by these agents, a better term could be, for instance, non-drug-induced autoimmune hepatitis. Drug cessation and immunotherapy with corticosteroids and azathioprine comprise the treatment of choice. The characteristics of DIAIH can best be described if both the RUCAM and the simplified AIH score are used concomitantly. Full article

Human T-lymphotropic virus 1 (HTLV-1) infection has been associated with inflammatory, autoimmune, and lymphoproliferative diseases with a wide spectrum of clinical manifestations. Among patients with inflammatory rheumatological disease manifestations, cases of rheumatoid arthritis, Sjögren’s syndrome, polymyositis, and fibromyalgia, among others, have been reported. Another common feature of rheumatological diseases is the presence of joint manifestations, such as arthralgia and arthritis. In the present study, we sought to determine the laboratory profile and clinical rheumatological manifestations of people living with HTLV-1/2 residing in a metropolitan area in the Brazilian Amazon. A total of 957 individuals were screened for HTLV-1/2 infection by enzyme-linked immunosorbent assay (ELISA), and samples from seropositive individuals were subjected to infection confirmation by Western blotting or quantitative polymerase chain reaction (qPCR). Individuals with confirmed HTLV-1 and HTLV-2 infection were clinically evaluated for signs and symptoms of rheumatological diseases. Of the 957 individuals tested, 69 were positive for HTLV-1/2 infection, with 56 confirmed cases of HTLV-1 infection (5.9%), 12 of HTLV-2 infection (1.2%), and 1 classified as undetermined (0.1%). After clinical screening, 15 infected individuals with complaints suggestive of rheumatological disease were selected for evaluation by a rheumatologist (11 with HTLV-1 infection (1.1%) and 4 with HTLV-2 infection (0.4%)). The predominant pain pattern was symmetrical polyarthralgia, with large joints predominantly being affected. The diseases diagnosed were psoriatic arthritis, osteoarthritis, fibromyalgia, and regional pain syndromes. Antinuclear antibody (ANA) positivity was observed in two patients. Our findings confirm that HTLV-1 infection is associated with rheumatological disease manifestations and highlight the novel finding of cases of HTLV-2 infection in patients with rheumatoid arthritis symptoms. Full article

Lung involvement is the most common extraglandular manifestation of primary Sjögren’s Disease (pSjD). There is an increasing interest in finding the clinical/serological risk predictors of this feature. A cross-sectional study evaluating anti-SSA/Ro antibodies, anti-SSB/La antibodies, rheumatoid factor, antinuclear antibodies, and the diffusing capacity of the lungs for carbon monoxide (DLCO) in 26 pSjD patients who presented interstitial changes on the chest CT scan was performed. The titres and positivity rates for anti-SSA/Ro (p = 0.02, p = 0.02) and anti-SSB/La antibodies (p = 0.01, p = 0.001) proved to be significantly increased in patients with abnormal DLCO. Anti-SSB/La antibodies’ titres seemed to be the best predictor for decreased DLCO–AUC 0.791 (0.587–0.994), p = 0.016. A close-to-significance decrease was found in the titres (p = 0.07) and positivity rates—p = 0.09 and OR of 0.15 (0.01–1.63)—of anti-SSB/La antibodies in patients with usual interstitial pneumonia (UIP), indicating their possible protective role against UIP. The lymphocytic interstitial pneumonitis (LIP) pattern on lung CT scan was significantly associated with the simultaneous positivity of the four examined serological markers (p = 0.03). The increase in anti-SSB/La antibody positivity rate in patients with LIP patterns was situated close to the significance level (p = 0.09). Quadruple positivity, as well as isolated anti-SSB/La positivity, could be risk factors for developing LIP in pSjD patients. Thus, anti-SSB/La antibodies might represent a marker of lung involvement in pSjD patients. Full article

Sjogren’s disease (SjD) is a systemic autoimmune disease primarily affecting the exocrine glands. Systemic manifestations, including hepatic involvement, are increasingly recognized. This study aimed to delineate the clinical features and associated factors of autoimmune hepatic involvement in SjD. A retrospective analysis was conducted on patients diagnosed with SjD at Seoul St. Mary’s Hospital over the past 10 years. Autoimmune hepatic involvement was defined by fulfilling diagnostic criteria for autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC). Clinical, serological, and demographic data were obtained from medical records. Among 1119 patients with SjD, 51 (4.6%) had autoimmune hepatic involvement. AIH (64.7%) was the most common type, followed by PBC (27.5%) and overlapping disease (7.8%). Compared to those without hepatic involvement, affected patients were older at diagnosis (p = 0.003) and showed higher frequencies of thrombocytopenia, splenomegaly, anti-centromere antibody (ACA), and elevated antinuclear antibody titers as measured by indirect immunofluorescence (IFI-HEp-2) (all p < 0.001). Multivariable analysis identified splenomegaly, elevated IFI-HEp-2 titer, and ACA positivity as independent factors associated with hepatic involvement. Most patients responded well to immunosuppressive therapy, with only a small proportion (15.7%) progressing to liver fibrosis. Autoimmune hepatic involvement is relatively uncommon but clinically meaningful in patients with SjD. Full article

The most serious complications of systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) include lung fibrosis (LF) and pulmonary hypertension (PH). The aim of this study was to find any association between the serological profile and the incidence of these complications. The tested group included 121 persons (87 SSc, 34 MCTD); mean age 55.6 ± 13.4 years. Patients were qualified for the LF presence group based on HRCT. Likelihood of PH was determined using echocardiography. The presence of antinuclear antibodies (ANA) was assessed using indirect immunofluorescence, ANA-profile, sclerosis-profile (using EUROIMMUN kits), and antiphospholipid antibodies (aPL) (using the ELISA method). Distribution of individual antibody types was at a level similar to the previously described groups in the Polish population and differed from the American and African population. A positive correlation was found between LF and the presence of anti-Scl-70 (p = 0.024) antibodies, negative correlation was found between LF and the presence of anti-histone (p = 0.03), anti-centromere A (p = 0.009), anti-centromere B (p = 0.014), and anti-nucleosomes (p = 0.03) antibodies. No correlation between the presence of aPL and the above complications was found. The prevalence of individual antibody types in SSc and MCTD may have ethnic and geographical grounds. Scl-70 antibodies correlate positively with LF. Anti-centromere, anti-histone, and anti-nucleosome antibodies reduce its risk. No correlation between aPL and the occurrence of LF and elevated PH risk was found. Full article

Background: Silicone breast implants have been linked to autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This study evaluates the role of ^99mTc-HYNIC-TOC somatostatin receptor scintigraphy in assessing somatostatin-mediated inflammation and the impact of explantation on inflammatory activity. Methods: Fifty patients with silicone breast implants and symptoms suggestive of ASIA were evaluated. Pre- and postexplantation imaging was performed using ^99mTc-HYNIC-TOC scintigraphy. Matthews correlation coefficients quantified associations between clinical symptoms and imaging findings, and autoantibody profiles were analysed. Results: Scintigraphy identified a significant uptake in organs associated with autoimmune symptoms, particularly joints and salivary glands. Strong correlations were found between imaging findings and symptoms, including knee pain (MCC = 0.81) and sicca syndrome (MCC = 0.96). Explantation resolved abnormal uptake in the surgical bed, though variable uptake persisted in other organs, reflecting systemic inflammatory heterogeneity. Autoantibody analysis revealed positivity in 66% of patients, with antinuclear antibodies being most frequent (30%). Conclusions: ^99mTc-HYNIC-TOC scintigraphy effectively evaluates organ-specific inflammation in ASIA. Explantation reduces localized inflammation but does not consistently address systemic autoimmune responses. Larger prospective studies are needed to validate these findings and improve management strategies for ASIA. Full article

Background and Objectives: Psoriatic arthritis (PsA) is a chronic rheumatic disease that is frequently associated with fibromyalgia (FM). The coexistence of FM complicates the evaluation of PsA disease activity and the planning of treatment strategies, as the two conditions share many overlapping clinical symptoms. To investigate the contribution of demographic factors and available serum biomarkers of inflammation and autoimmunity in characterizing the heterogeneity among patients meeting the classification criteria for both PsA and FM. Materials and Methods: This cross-sectional, single-center study involved 1547 adult patients evaluated between January 2017 and December 2024 who met the CASPAR criteria for PsA. A patient subgroup also met the 2016 ACR criteria for FM. Demographic data, serum inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and autoimmunity markers including antinuclear antibodies (ANA), rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA) were evaluated. Statistical analyses included chi-square tests, t-tests, Mann–Whitney U tests, and multivariate logistic regression to identify independent predictors associated with the coexistence of PsA and FM. Results: A total of 254 patients (16.42%) were diagnosed with concomitant FM. Compared to patients with PsA alone, those with concurrent PsA and FM showed significantly lower C-reactive protein (CRP) levels (0.39 ± 0.74 vs. 2.88 ± 12.31 mg/dL; p < 0.001) and a higher frequency of antinuclear antibody (ANA) positivity (13.57% vs. 5.78%; p < 0.001). No significant differences were observed in rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) positivity between the groups. Multivariate logistic regression identified female sex, ANA positivity, CRP levels ≤ 0.5 mg/dL, and elevated body mass index (BMI) as independent predictors of the presence of concomitant FM. Conclusions: Patients with concomitant PsA and FM have a distinct demographic and serological profile, suggesting the existence of a clinically significant subgroup within the PsA population. Recognition of these differences may improve diagnostic accuracy and support the development of personalized, non-immunosuppressive therapeutic strategies for this subgroup of patients. Full article

The number of metabolic dysfunction-associated steatotic liver disease (MASLD) patients is increasing rapidly. More attention has been paid to the relationship between immunity and MASLD. This study explored the roles of serum autoantibodies, immunoglobulins, and complements in MASLD. A total of 182 MASLD patients were investigated and grouped by autoantibody or NAS scores. Correlation between immunology and clinical features was assessed. In addition, metabolic dysfunction-associated steatohepatitis (MASH) models were constructed to verify the findings. Neutrophils were isolated from mice and treated with complement C3 to investigate the association between C3 and neutrophil extracellular traps (NETs). IgG, IgM, and NAS scores in the autoantibody positive group were significantly higher than those in the autoantibody negative group. Antinuclear antibodies (ANA), IgA, IgE, IgG, C3, C4, ALT, and AST were related to MASH. Meanwhile, IgA and C3 correlated with the severity of MASLD. The ROC curve showed that IgA > 2.990 g/L or C3 > 1.115 g/L predicted the presence of MASH. More importantly, IgG, activated C3, and NETs were increased in MASH. C3 stimulation directly induced NET formation in the neutrophils. Immunity systems were activated in MASH and elevated IgG activated C3 to stimulate the production of NETs, thus exacerbating MASH. Full article

A 67-year-old male with metastatic human papillomavirus (HPV)-positive oropharyngeal cancer receiving pembrolizumab (anti-programmed cell death protein 1 [PD-1] immune checkpoint inhibitor) presented with bilateral ocular dryness. It is important to note that these symptoms appeared eight months after the initiation of the pembrolizumab therapy. Ophthalmologic evaluation revealed keratoconjunctivitis sicca with characteristic bulbar fluorescein staining and the Schirmer test showed 0 mm bilaterally. Serological testing demonstrated positive antinuclear and anti-SSb/La antibodies, consistent with Sjögren’s syndrome as an immune-related adverse event (irAE). Treatment with topical fluorometholone 0.1% and diquafosol 3% led to complete symptom resolution within one year while maintaining cancer immunotherapy. Long-term follow-up over 3.5 years demonstrated sustained ocular improvement and a favorable oncologic response without development of systemic autoimmune manifestations. This case highlights that Sjögren’s syndrome as an irAE may present with isolated ocular manifestations, which could be overlooked in clinical practice. Full article