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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 < 0.0001). The proportion of positive results in the 4 age groups analyzed: 0-19, 20-39, 40-59, and ≥ 60 years was 23.3, 20.2, 20.1, and 22.8%, respectively (p < 0.0001). Considering all positive sera (n = 11,478), AC-4 nuclear fine speckled (37.7%), AC-2 nuclear dense fine speckled (21.3%), BAC-3 nuclear quasi-homogeneous (10%) and mixed/composite patterns (8.8%) were the most prevalent patterns. The specialties that most requested HEp-2-IIFA were general practitioner (20.1%), dermatology (15%), gynecology (9.9%), rheumatology (8.5%), and cardiology (5.8%). HEp-2-IIFA positivity was higher in patients referred by rheumatologists (35.7% vs. 19.6%) (p < 0.0001). Moderate (46.4%) and high (10.8%) titers were more observed in patients referred by rheumatologists (p < 0.0001). We observed a high proportion of mixed and cytoplasmic patterns in samples referred by oncologists and a high proportion of BAC-3 (nuclear quasi-homogeneous) pattern in samples referred by pneumologists., Conclusions: One-fifth of the patients studied were HEp-2-IIFA-positive. The age groups with more positive results were 0-19 and ≥ 60 years. AC-4, AC-2, BAC-3 and mixed/composite patterns were the most frequent patterns observed. Rheumatologists requested only 8.5% of HEp-2-IIFA. Positive results and moderate to high titers of autoantibodies were more frequent in patients referred by rheumatologists., (© 2022. The Author(s).)

Abstract While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.

The aim of the study was to find out the pattern of IgM and IgG changes in patients with autoimmune thyroiditis depending on the pathological process duration. Materials and methods. A single-center cross-sectional study with randomization elements enrolled 170 patients with autoimmune thyroiditis, and 65 patients without thyroid pathology or other autoimmune diseases were assigned to sex- and age-matched comparison group (p = 0.6155 and p = 0.3093, respectively). The patients were classified according to thyroid status parameters into subclinical and manifest groups. All study participants were examined on IgM and IgG levels based not only on the clinical form of the disease, but also on the disease duration (up to 5 years and more than 5 years). The control group comprised 65 healthy individuals, including 26 men and 39 women (mean age 38.7 ± 10.8 years). Results. A slight decrease in IgM levels was observed in patients with subclinical form and longer disease duration, which was 1.5 (1.5; 1.7) g/l with the disease duration of up to 5 years and 1.4 (1.2; 1.4) g/l with the disease duration of more than 5 years, while there were no differences in IgM levels in patients with manifest form with longer disease duration. IgG concentrations were statistically significantly higher in both clinical groups of patients with the disease duration of up to 5 years compared to those in patients with the disease duration of more than 5 years (13 (11; 14) g/l up to 5 years and 11 (10; 12) g/l more than 5 years in subclinical group, p < 0.05); 13 (12; 14) g/l up to 5 years and 12 (10; 15) g/l more than 5 years in manifest group, p < 0.05). Conclusions. A downward trend in IgG concentrations is noted with the disease progression and longer duration, while IgM levels are uninformative.

Objective To analyze a case of hyperhemolytic syndrome(HHS) and explore the laboratory diagnostic method and clinical treatment strategy. Methods Serological tests such as blood typing, direct antiglobulin test(DAT), anti-screening and antibody identification were performed, The complete blood count(CBC), as well as hemolysis indicators such as lactate dehydrogenase(LDH) and bilirubin were tested, and the changes and progression of hemolysis were monitored.By using genotyping methods to test 32 common rare blood type antigens in clinical practice, the accuracy of antibody identification results was supported. Results The patient had anti-E antibodies and autoantibodies in her serum. After blood transfusion, LDH and bilirubin increased significantly, but hemoglobin dropped sharply, far lower than before transfusion, presenting with unique manifestations such as hemoglobinuria.The patient made a full recovery after treatment with high-dose intravenous immunoglobulin and corticosteroids. Conclusion HHS is a rare and potentially fatal diseases, which is mainly manifested by hemolysis and severe anemia, and the hemoglobin level after blood transfusion is often lower than that before blood transfusion. This patient had typical clinical manifestations of post-transfusion hyperhemolytic reaction. After timely and correct treatment, the patient recovered completely and was discharged, accumulating valuable clinical experience for the diagnosis and treatment of such disease.

Autoimmune Haemolytic Anaemia (AIHA) occurs when an individual’s immune system produces autoantibodies against antigens on Red Blood Cells (RBCs). It is a relatively rare haematological disease in the paediatric population. Case reports of paediatric warm AIHA are rare in general and are usually associated with other underlying conditions like haematological neoplasms, viral infections, and drug-induced conditions. This is a case report of a three-year-old male child with warm AIHA who presented with dark urine and decreased urine output for one day. Through laboratory and radiological investigations, it was found that this patient developed acute haemolysis following a bacterial lower respiratory tract infection. The patient was treated with corticosteroids, antibiotics, and Intravenous Immunoglobulins (IVIg). Peritoneal dialysis was also done. The patient was eventually discharged from the hospital on a maintenance dose of oral steroids, which was gradually tapered off. It was concluded that a bacterial lower respiratory tract infection can lead to warm AIHA in children. Even though this illness is rare, it may cause life-threatening complications if prompt treatment is delayed.

Abstract Psoriasis is a chronic inflammatory disease that sometimes necessitates therapeutic intervention with biologics. Autoantibody production during treatment with tumor necrosis factor (TNF) inhibitors is a recognized phenomenon, however, the production of autoantibodies associated with antiphospholipid syndrome (APS) has not been comprehensively evaluated in patients with psoriasis. This study was conducted to assess the prevalence of APS-associated autoantibodies in patients with psoriasis treated with different biologics and to investigate the potential associations between autoantibody production and clinical or serological parameters. Patients with psoriasis undergoing biologics treatments were enrolled in this study, and were categorized based on the type of biologics administered, TNF, interleukin (IL)-17, or IL-23 inhibitors. Clinical and serological data were collected and analyzed in conjunction with data on APS autoantibodies. TNF inhibitors were associated with a higher frequency of APS autoantibodies compared to IL-17 and IL-23 inhibitors. Notably, the presence of APS autoantibodies correlated with concurrent arthritis and higher disease severity at treatment initiation in patients treated with TNF inhibitors. Elevated Psoriasis Area and Severity Index scores and anti-nuclear antibody titers higher than × 320 were predictors of APS autoantibody production. Despite the higher autoantibody rates, clinical symptoms of APS were absent in these patients. This study provides the first comprehensive evidence of an increased frequency of APS autoantibodies associated with TNF inhibitor treatment in patients with psoriasis. The observed association between APS autoantibody positivity and TNF inhibitor treatment or clinical parameters suggests a potential immunomodulatory interplay between autoimmunity and inflammation in the pathogenesis of psoriasis.

Introduction: Systemic lupus erythematosus (SLE), the commonest type of lupus, is an autoimmune multisystemic disorder that can affect any organ system of the body, especially blood vessels and connective tissues, causing widespread inflammation. Pediatric onset of SLE is a rare condition with more hematological involvement. Aim: This study was undertaken to observe various hematological abnormalities and their association with various autoantibodies present in pediatric SLE in Eastern India. Methodology: It was a single-centered, cross-sectional, observational, hospital-based study conducted in the Department of Pediatric Medicine in collaboration with the Department of Rheumatology in IPGME and R and SSKM Hospital, Kolkata. The duration of the study was 1.5 years, and a total of 30 children up to 12 years of age of either gender were enrolled. Study participants were evaluated for various parameters like demographic, hematological (anemia, neutropenia, leucopenia, lymphopenia, and thrombocytopenia), biochemical (CRP, Lactate dehydrogenase (LDH), and bilirubin), autoantibodies (anti-dsDNA, anti-Ro 52, and anti-Ribonucleoprotein [RNP]), and SLE related pathologies (Cutaneous, nephritis, serositis). Results: In the present study, most of the participants had arthritis, muscle pain (86.66%), and hematological involvement (80%). Among cytopenias, anemia was the commonest. dsDNA autoantibody was positive in most of the patients (83%), and about one-third suffered from autoimmune hemolytic anemia (AIHA). No association was observed between autoantibodies and various hematological manifestations. Conclusion: It can be concluded from the present study that anemia is the most common cytopenia in pediatric SLE, but there is no association between autoantibodies and these cytopenias. However, study on larger population may give better results.

Objectives Autoantibody-negative RA differs from autoantibody-positive RA in several clinical aspects, possibly underpinned by pathogenetic differences. At present, the role of adaptive immune responses in autoantibody-negative RA remains unclear. Here, we investigated the synovial and serum immunophenotype indicative of B lymphocyte involvement across the spectrum of autoantibody-positive and -negative chronic arthritides. Methods Ultrasound-guided synovial biopsies were retrieved from 131 patients: 43 autoantibody-positive RA, 35 autoantibody-negative RA, 25 polyarticular PsA and 28 oligoarticular PsA. Samples were analysed for the degree of histological inflammation, B lymphocyte infiltration and the distribution of different pathotypes (lympho-myeloid, myeloid, pauci-immune). Serum levels of the B cell chemoattractant CXCL13 were compared among groups. Results Synovitis scores and CD68+ sublining macrophage infiltration were comparable irrespective of clinical diagnosis and disease subtype. In contrast, the degree of B lymphocyte infiltration and the frequency of lympho-myeloid synovitis in autoantibody-negative RA were lower than those of autoantibody-positive RA (mean [ s. d.] 1.8 [1] vs 2.4 [0.6], P  = 0.03, and 38.2% vs 62.9%, P  = 0.07, respectively), and similar to polyarticular PsA. Oligoarticular PsA had the lowest B cell scores. Serum CXCL13 was associated with lympho-myeloid synovitis and followed a similar gradient, with the highest levels in autoantibody-positive RA, intermediate and comparable levels in autoantibody-negative RA and polyarticular PsA, and low levels in oligoarticular PsA. Conclusions The synovial and serum immunophenotype indicative of B lymphocyte involvement in autoantibody-negative RA differs from that of autoantibody-positive RA and more closely resembles that observed in polyarticular PsA. The pathobiological stratification of chronic inflammatory arthritides beyond clinical diagnosis may fuel personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to describe adult Brazilian and Japanese patients with anti-small ubiquitin-like modifier activating enzyme (SEA)-positive dermatomyositis (DM), as there are few studies in the literature. A literature review was also conducted. Methods. This bicentric international retrospective study, conducted between 2012 and 2023, included patients with anti-SAE-positive DM (2017 European League Against Rheumatism/American College of Rheumatology classification criteria). All demographic features and clinical, laboratory, therapeutic, and follow-up data were collected from Brazilian and Japanese centers using pre-standardized and parameterized information. Results. We included 17 adult patients with a median age of 65 (56-76) and a predominance of females (82.4%). Constitutional symptoms at baseline were present in 58.8% of the patients. In addition to classical cutaneous DM lesions, one-third of the patients had myalgia and significant muscle weakness, whereas half presented with dysphagia, interstitial lung disease, and joint manifestations. The first-line treatment consisted of intravenous methylprednisolone and immunoglobulin pulse therapy in 41.2% and 28.6% of the patients, respectively. The median follow-up duration was 20 (13-74) months; at the last medical evaluation, half had active disease and were still using oral glucocorticoids (median dosage, 10.0 mg/day). Approximately one-fifth to one-third of the patients were diagnosed with different types of cancer, had severe infections, or died. Conclusions. Patients with anti-SAE-positive DM not only resemble the phenotype of antisynthetase syndrome but are also associated with a poor prognosis.

Coeliac Disease (CD) and Sjogren’s Syndrome (SS), both autoimmune disorders, are gaining attention for their complex interaction when occurring together. CD involves gluten intolerance and can present with gastrointestinal symptoms, while SS affects various organs, primarily causing dryness of the eyes and mouth. Diagnosis for each relies on specific criteria including serologic testing and histopathology. When these conditions overlap, they create unique clinical challenges, highlighting the need for a thorough understanding of their combined effects on health. This exploration aimed to uncover the intricacies of their relationship, including clinical manifestations and implications for diagnosis and management when dealing with both simultaneously. In both cases (58-year-old female and 47-year-old female), there was gastrointestinal villous atrophy as a manifestation of CD, which improved with simple dietary modification.

Lupus Anticoagulant (LAC) is a group of auto antiantibodies that interfere with phospholipid dependent tests like Activated Partial Thromboplastin time (APTT) and dilute Russell Viper venom time (dRVVT) on in vitro basis. LA, anti cardiolipin antibodies (aCL) IgG/IgM, and anti-β2 glycoprotein I antibodies [aβ2GPI]IgG/IgM are three diagnostic criteria for laboratory diagnosis of anti-phospholipid antibodies (aPL). The circulating aPLs in the clinical setting of hypercoagulability state or adverse pregnancy outcomes is termed as anti-phospholipid syndrome (APS). The laboratory diagnosis of APS is complicated, it includes constellation of tests like solid phase immunoassays for measurement of aCL and a β 2GPI by and coagulation based assays for detection of LAC. LAC diagnosis is especially challenging in the setting of anti-coagulation therapy, numerous modifications to circumvent this interference have rendered success. The Thrombin generation assays [TGA] for LAC detection and estimation of LAC pathogenicity are available but are yet to be accepted as routine laboratory tests. The medley of assays like Enzyme-linked immunosorbent and chemiluminescent assays are available for detection of aCL and aβ2GPI but due to the non-availability of universal calibrators and standards there is lack of harmonization between various solid phase assays. In this article we intend to highlight new recommendations of laboratory diagnosis of LAC with special emphasis on diagnosis in the setting of pregnancy and anti-coagulation. For risk assessment in APS other non-criteria aPL like as anti-domain β2 glycoprotein I and anti-phosphatidyl serine/prothrombin antibodies are under evaluation. There is an ongoing quest towards harmonization of detection of LAC, thus there has been succession of guidelines to meet the challenges and incorporate newly found knowledge every time, namely International Society for Thrombosis and Hematology- Scientific Standardization Committee (ISTH-SSC) guidelines, followed by British Committee for Standards in Hematology (BCSH), Clinical and Laboratory Standards Institute (CLSI) guidelines 2014 and finally guidelines/updates issued by ISTH- SSC in 2018.

The aim of the study was to examine the involvement of tissue-specific and non-specific autoantibodies, matrix metalloproteinase-3 and neuron-specific enolase (NSE) enzymes in the development and exacerbation of autoimmune thyroiditis. Materials and methods. The study enrolled 170 patients with autoimmune thyroiditis (64 males and 106 females aged 18 to 64 years) to comprehensively examine their humoral immune response indicators (IgA, M, G), organ-specific (Ab-TG, Ab-TPO) and organ-non-specific antibodies (Ab-DNA), metalloproteinase-3 and NSE activity. The control group consisted of 65 individuals without thyroid pathologies or other autoimmune diseases, aged 20 to 65 years (26 males and 39 females). Results. The study has demonstrated changes in the levels of organ-specific and organ-nonspecific antibodies and statistically significantly increased metalloproteinase-3 activity in patients with autoimmune thyroiditis. Positive correlations have been found between elevated levels of IgG, Ab-TG, Ab-TPO, Ab-dsDNA and NSE activity. Negative correlations have been observed between NSE activity and IgA concentrations. Conclusions. Elevated titers of anti-DNA autoantibodies may indicate an aggravation of the autoimmune process due to cellular structure damage, resulting in gland dysfunction. The findings also suggest that metalloproteinase-3, a marker predicting thyroid tissue damage, may negatively impact the immune response induction, ultimately affecting the activity of neuron-specific enolase. The data have shown that studying biochemical indicators such as antinuclear antibodies (ANA), anti-DNA antibodies, metalloproteinase-3 and neurodegenerative indicators could provide informative markers to determine the nature of the disease development and worsening.

Key Clinical Message This case underscores the critical importance of timely recognition and management of NMDAR encephalitis in adolescents to mitigate potential long‐term sequelae. If a pediatric patient presents with suspected viral encephalitis, autoimmune etiology must be excluded via cerebrospinal fluid antibody assay to guide appropriate immunosuppressive therapy, and improve patient outcomes. Abstract Autoimmune encephalitis particularly involving the n‐methyl‐d‐aspartate receptor (NMDAR) is recognized as a rare cause of acute encephalopathy in pediatric patients. The following case is of a 14‐year‐old female diagnosed with anti‐NMDAR encephalitis who initially presented with fever, episodic convulsions, and loss of consciousness. She subsequently developed right‐sided body weakness, expressive aphasia, and visual hallucinations. Clinical examination revealed prominent neuropsychiatric manifestations such as altered sensorium, motor deficits, hallucinations, and visual disturbances. Cerebello‐bulbar signs were not appreciable in this particular case. She was treated for viral encephalitis but showed no improvement. Laboratory investigations revealed the presence of NMDAR antibodies in the cerebrospinal fluid confirming the diagnosis of autoimmune etiology. The patient demonstrated notable improvement following immunosuppressive treatment.

Objective To investigate the changes in serum thyrotropin receptor antibody (TRAb), thyroid stimulating antibody (TSAb), and thyroid-stimulating blocking antibody (TSBAb) and their significance in patients with Hashimoto’s thyroiditis with hypothyroidism (HT hypothyroidism). Methods A total of 133 patients with HT hypothyroidism (HT hypothyroidism group) and 125 healthy subjects (control group) were enrolled and their clinical data were collected. The serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), and TRAb were measured and compared between the two groups. TSAb and TSBAb were also compared across the patients who were positive for TRAb (group B), who were negative for TRAb (group C), and the healthy subjects who were negative for TRAb (group A). A Pearson correlation analysis was used to examine the relationships between the serum levels of TSAb and TSBAb and the serum levels of FT3, FT4, TSH, and TRAb in patients with HT hypothyroidism. Results The serum TRAb level in the HT hypothyroidism group was significantly higher than that in the control group (Z=-5.434,P

Autoimmunity and autoinflammation, co-potentiating pathological processes, are considered within the "immune-inflammatory" continuum (continuity with a variety of elements), reflecting the close relationship between the innate and acquired immune responses. Autoimmunity is the leading pathogenetic mechanism for a specific type of human chronic inflammatory disorders – autoimmune diseases, affecting more than 10% of people in the general population. Advances in molecular biology, pharmacogenetics, and bioinformatics provided the background for individualizing therapy for systemic autoimmune rheumatic diseases within personalized medicine. Studying the immunopathogenesis mechanisms, improving diagnostics, interpreting the molecular taxonomy, and developing approaches to the prevention and personalized therapy of systemic autoimmune rheumatic diseases are the priority issues of modern medicine.

AbstractObjective The aim of this study was to define the clinical, histopathologic, and prognostic features associated with simultaneous positivity for anti-dsDNA, -nucleosome, and -histone antibodies (3-pos) in Korean patients with biopsy-proven lupus nephritis (LN).Methods The 102 patients included in the study had undergone kidney biopsy prior to the start of induction treatment, were treated with immunosuppressives, and followed-up for >12 months.Results In total, 44 (43.1%) of the 102 LN patients were 3-pos. Patients with 3-pos had a higher SLEDAI-2K score (p = .002), lower lymphocyte count (p = .004), and higher rates of proteinuria > 3.5 g/24 h (p = .039) and positivity for urinary sediments (p = .005) at the time of renal biopsy than non-3-pos patients. 3-pos patients had a more proliferative form of LN (p = .045) in the renal histopathologic findings, and as co-positivity gradually increased from 0 to 3, the total activity score in the renal biopsy findings increased significantly (p = .033). In addition, 3-pos patients had a more rapid eGFR decline than non-3-pos patients after a follow-up of 83.2 months (p = .016).Conclusions Our findings suggest that 3-pos is related to severe LN and that 3-pos patients are more likely to experience a rapid decline of renal function than non-3-pos patients.KEY MESSAGEPatients with co-positivity for anti-dsDNA, -nucleosome, and -histone antibodies (3-pos) had higher disease activity and a worse renal histopathology than those without co-positivity.3-pos patients had a more rapid decline of renal function than non-3-pos patients.

Autoimmune Limbic Encephalitis is a rare disease occurring with a frequency of approximately 13.7/100,000 people, mainly among middle-aged women. The disease is caused by autoantibodies, either synthesised due to the presence of a tumour or having an idiopathic nature. Depending on the type of autoantibodies detected, the disease is divided into subtypes, which differ in the frequency of specific clinical symptoms (most commonly psychosis, mood changes, memory problems, cognitive impairment and seizures) and can direct to detection of a specific type of cancer. Making a prompt diagnosis and initiating treatment is crucial as it ensures a reduction in clinical symptoms and improves survival rate. Broad immunotherapy is used - intravenous immunoglobulin, corticosteroids, azathioprine, rituximab, cyclophosphamide, anti-epileptic drugs and plasmapheresis. The efficacy is high - 80% of patients recover, and relapses occur in only 10% of cases. If a patient is diagnosed with cancer, effective oncological treatment is necessary to achieve complete remission.

INTRODUCTION: Brucellosis is a chronic infectious disease with osteoarticular (OA) manifestations. It is difficult to distinguish between brucellosis and rheumatologic diseases in endemic areas. In this study, we aimed to report the clinical findings and autoantibody results of patients diagnosed with brucellosis in the rheumatology department. METHODS: In this study, 92 patients over the age of 18 with the diagnosis of "Brucellosis" were included. All patients' systemic and joint examinations were performed. In the presence of clinical signs, those with a detected value of ≥1: 160 on the standard tube agglutination test were considered to be active brucellosis. Those with arthritis, arthralgia, tenosynovitis-bursitis, spondylodiscitis and sacroiliitis were detected on examination or magnetic resonance imaging, and those with low back or hip pain were recorded. Complete blood count,C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and RF, anti-CCP, ANA and anti-DNA results were evaluated. RESULTS: The mean age of ninety-two patients (Female: 54, 58.7%) was 39.3+-13 years. In the OA findings; arthralgia was detected with a ratio of 90.2%, arthritis with 33.7%, myalgia with 28.2%, sacroiliitis with 25% and spondylodiscitis with 6.5%. CRP and ESR means were 19 mm/h with 2.1 mg\dL. RF was positive in 12 (13%), Anti-CCP in 5 (5.4%), ANA in 7 (7.6%).There were no patients with anti-DNA positivity. The median treatment duration was 12 weeks. DISCUSSION AND CONCLUSION: The anti-CCP positivity was lower than in the literature, and RF and ANA positivity were similar. Symmetrical involvement of small joints, higher CRP and high titer autoantibody positivity were at a higher risk of developing rheumatologic disease.

In patients with systemic sclerosis (SSc), interstitial lung disease (ILD) is a factor in the decline of functional capacity up to disability and is also the leading cause of death. Therefore, one of the most important tasks in the treatment of this group of patients is not only to detect involvement of respiratory system, but also to predict the likelihood of its development.Objective: to study the possibility of predicting the development of ILD and advanced ILD in patients with SSc.Material and methods. The study included 79 patients with SSc (mean age 64.4±11.5 years; 94.9% women) from the Registry of myositis, SSc and Mixed Connective Tissue Diseases (РЕМИССиС) who underwent high-resolution computed tomography (HRCT) of the lungs. Classification trees (CTr) were constructed to predict the development of widespread ILD using the CHAID algorithm (exhaustive). All patients were tested for antibodies against Scl-70 (anti-Scl-70), CENP-B (anti-CENP-B), and PmScl (anti-PmScl).Results and discussion. ILD signs according to HRCT were detected in 53 patients. Fibrotic (34.2%) and cellular (15.2%) types of nonspecific interstitial pneumonia were the most common, and common interstitial pneumonia was less frequent (11.4%).The presence of ILD and advanced ILD (involvement of more than 20% of the lung parenchyma) were significantly associated with the detection of any autoantibodies, except anti-centromere antibodies, an increase in pulmonary artery systolic pressure, a decrease in forced vital capacity, diffusing capacity of the lungs, blood oxygen saturation at rest, and all parameters of six-minute walk test (6MWT), and complaints of shortness of breath. In addition, the presence of extensive ILD was also significantly associated with diffuse SSc and with SSc without skin manifestations.In establishing the CTr, it was found that the development of widespread ILD was unlikely in individuals who were able to walk more than 440 m in 6MWT and had neither anti-Scl-70 nor anti-PmScl.Significant associations were also found between the radiological pattern of ILD and the types of disease-specific antibodies.Conclusion. The 6MWT data in conjunction with the results of testing for SSc-specific autoantibodies provide a very accurate prediction of the presence and extent of ILD. It is advisable to include these indicators in the algorithm for screening and monitoring patients with SSc.

Autoimmune polyendocrine syndromes (APSs), also called autoimmune polyglandular syndromes, are a group of autoimmune diseases characterized by the co-occurrence of dysfunctions of several (at least two) endocrine glands. They develop under the influence of environmental factors in genetically predisposed people. Autoimmune polyendocrine syndromes may accompany autoimmune rheumatic diseases and worsen their course – APS-2 and APS-3 are the most common. The APS-2 includes the coexistence of, e.g. Hashimoto’s disease, celiac disease and rheumatoid arthritis (RA). In APS-3, rheumatic diseases such as RA, systemic lupus erythematosus, and Sjögren’s syndrome may coexist with Hashimoto’s disease, type 1 diabetes and hypogonadism or other endocrinopathies. Undiagnosed endocrine diseases may be the reason for the intensification of metabolic disorders observed in the course of rheumatic diseases, cause the ineffectiveness of rheumatological treatment and also increase the frequency of bone fractures due to osteoporosis, cardiovascular complications and even miscarriages when coexistent, e.g. Hashimoto’s disease with hypothyroiditis, which increases the risk of pregnancy loss. It is important to be able to conduct an extensive interview, paying attention to the symptoms of possible endocrinopathy as well as the features of other autoimmune disorders in the physical examination (e.g. vitiligo or darkening of the skin in Addison’s disease). Depending on the history and physical examination, screening for various APSs is advised.

Background/Aims This study aimed to investigate the clinical characteristics and outcomes of fluorescent antinuclear antibody (FANA)-positive patients admitted for coronavirus disease 2019 (COVID-19) and identify FANA as a prognostic factor of mortality. Methods This retrospective study was conducted at a university-affiliated hospital with 1,048 beds from September 2020 to March 2022. The participants were consecutive patients who required oxygenation through a high-flow nasal cannula, non-invasive or mechanical ventilation, or extracorporeal membrane oxygenation, and conducted the FANA test within 48 hours of admission. Results A total of 132 patients with severe COVID-19 were included in this study, of which 77 (58.3%) had FANA-positive findings (≥ 1:80). FANA-positive patients were older and had higher inflammatory markers and 28-day mortality than FANA-negative patients. In the multivariate Cox proportional hazard regression analysis, FANA-positive findings (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.04–6.74), age (per 1-year; HR, 1.05; 95% CI, 1.01–1.10), underlying pulmonary disease (HR, 3.16; 95% CI, 0.97–10.26), underlying hypertension (HR, 2.97; 95% CI, 1.28–6.87), and blood urea nitrogen > 20 mg/dL (HR, 3.72; 95% CI, 1.09–12.64) were independent predictors of 28-day mortality. Remdesivir (HR, 0.34; 95% CI, 0.15–0.74) was found to be an independent predictor that reduced mortality. Conclusions Our findings revealed an autoimmune phenomenon in patients with severe COVID-19, which provides an ancillary rationale for strategies to optimize immunosuppressive therapy. In particular, this study suggests the potential of FANA to predict the outcomes of COVID-19.

Latent autoimmune diabetes in adults (LADA) is a slow progressive autoimmune destruction of pancreatic beta cells. This condition tends to manifest during adulthood, often around 35 years of age. While LADA can initially be managed by oral medications, eventually the patient will require insulin. We report a case of a 34-year-old woman who was initially treated for type 2 diabetes mellitus but was later diagnosed with LADA.

This case report describes the finding of EDTA-dependent Pseudothrombocytopenia in an 8-month-old infant, an extremely rare condition not reported in the literature. The patient presented with a fever due to insect bite and was diagnosed with abscessed cellulitis. A complete blood count showed a thrombocytopenia of 47 mil/L, with no history of bleeding or hematologic disease. The following day a new test was performed, which showed a platelet count of 214 mil/L, which was not consistent with the expected evolution of a real thrombocytopenia. Pseudothrombocytopenia was suspected and confirmed by observing platelet aggregates in the blood smear and upon recounting in a tube with sodium citrate, showed a normal value of 298 mil/L. Treatment consists of avoiding the use of EDTA as an anticoagulant and using other anticoagulants such as citrate or heparin. Timely identification of this phenomenon is essential to avoid diagnostic confusion and unnecessary or harmful treatment. This case brings to the scientific literature an example of EDTA-dependent Pseudothrombocytopenia in a pediatric patient, which can be easily confused with other causes of thrombocytopenia and requires a high index of clinical suspicion.

The pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissues from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy. Employing human and Escherichia coli K12 proteome arrays, we profiled the antibodies extracted from explanted SAH, livers with other diseases, and HD livers. Compared with their counterparts extracted from livers with other diseases and HD, antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins and E. coli antigens. Further, both Ig- and E. coli-captured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion, and focal adhesion (IgG). Except IgM from primary biliary cholangitis livers, no common autoantigen was recognized by Ig- and E. coli-captured Ig from livers with other diseases. These findings demonstrate the presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in SAH livers.

ABSTRACT Objective Published studies have shown associations between anti-ribosomal P (anti-P) antibody and systemic lupus erythematosus with hepatic manifestations. This has been reported also in autoimmune hepatitis. However, the consistency of the latter association remains controversial. This study aimed to evaluate the frequency of anti-P antibodies in autoimmune hepatitis using two different immunoassays. Methods One-hundred and seventy-seven patients with autoimmune hepatitis were screened, and 142 were analyzed for anti-P antibody positivity. The samples were first analyzed using two different immunoassays: enzyme-linked immunosorbent assay (ELISA) and chemiluminescence and then compared with a group of 60 patients with systemic lupus erythematous. The positive samples were subjected to western blot analysis. Results Anti-P was found in 5/142 autoimmune hepatitis cases (3.5%) by chemiluminescence and in none by ELISA. Among the five chemiluminescence-positive autoimmune hepatitis samples, on anti-P western blot analysis one was negative, two were weakly positive, and two were positive. In contrast, anti-P was detected in 10/60 patients with systemic lupus erythematosus (16.7%) and presented higher chemiluminescence units than the autoimmune hepatitis samples. Conclusion A low frequency of anti-P antibodies was observed in autoimmune hepatitis, suggesting that this test is not useful for the diagnosis or management of this disease.

Objective: To identify auto-antibodies in systemic sclerosis with interstitial lung disease (ILD). Method: This was a descriptive categorical study on auto-antibody profile in systemic sclerosis patients visiting the Rheumatology Clinic of Dr. Hasan Sadikin General Hospital, West Java, and Bandung during the period of January 2018 to December 2019 who were registered in the West Java Systemic Sclerosis Registry. Auto-antibody identification was performed using the Euroline immunoblot assays. Results: Thirty six cases were identified during the study period with most of the cases involved women (n=35, 97.2%). The average age of patients participating in this study was 40 years, with an average duration of disease of 18 months. Diffuse cutaneous systemic sclerosis was found in 22 (61.1%) cases and limited cutaneous systemic sclerosis was observed in 14 (38.9%) cases. Specific autoantibodies were positive in 33 (91.6%) cases, with anti-topoisomerase I as the largest group, positive in 22 (52.9.3%) cases. This was followed by anti-Th/To in eight (15.7%) cases; anti-Ro52 in four (7.8%) cases; anti-centromere in three (5.9%) cases; anti-RNA polymerase in three (5.9%) cases; anti-fibrillarin in three (5.9%) cases; anti-Ku in two (3.9%) cases; and anti-PDGF in one (2.0%) case. High-resolution computed tomography of the lung showed 34 (94.4%) cases with ILD and 22 (61.1%) cases with severe lung fibrosis. Usual interstitial pneumonia was seen in 19 (52.8%) cases and non-specific interstitial pneumonia in 15 (41.7%) cases. Conclusion: Anti-topoisomerase I, anti-Th/To, and anti-Ro52 are the most common autoantibodies observed in systemic sclerosis patients with ILD as the most prevalent feature detected with lung HRCT.

Relevance . Despite the large list of biological markers of cardiovascular diseases, not all have evidence-b ased effectiveness and independent prognostic value. Laboratory diagnostics of serum cardiospecific auto-antibodies for the diagnosis of myocyte cell damage has several potential advantages compared to the evaluation of traditional methods. These include the analysis of natural globulins to troponin I (cTnI), to alpha-a ctin 1 (ACTC1), to the heavy chain of beta-myosin 7B (MUN7B), which are based on a self-sustaining immune response to the myocardium’s own auto-antigens, which leads to damage to the cells expressing them. Purpose: To determine the diagnostic and practical value of quantitative indicators for the autoantibody complex to cardiomyocyte proteins to troponin I, to alpha-a ctin 1 and to the heavy chain of beta-myosin 7B in patients with cardiac pathology. Materials and Methods. The study of auto-antibodies to cTnI, ACTC1 and MUN7B in blood serum using laboratory enzyme immunoassay was carried out in patients with cardiac pathology undergoing inpatient treatment at the Regional Clinical Cardiology Dispensary in Stavropol. Additionally, an instrumental and laboratory examination was carried out in accordance with the clinical recommendations developed by the Association of Cardiovascular Surgeons, the Cardiological Society of Russia and approved by the Scientific and Practical Council of the Ministry of Health of the Russian Federation. The work was examined and approved by the Ethics Committee of the North Caucasus Federal University. Results and Discussion . Changes in the level of autoantibodies to cTnI, ACTC1 and MUN7B proteins in blood serum were statistically significant (p 0.01 v. s. p 0.01). A persistent increase in the level of auto-antibodies to cTnI by 2.36 ng/ml (694.11 %), to ACTC1 by 3.6 ng/ml (141.73 %) and to MUN7B by 1.74 ng/ml (119.17 %) was found in individuals with confirmed cardiac pathology, when other criteria for laboratory analysis were within acceptable values, which determine their diagnostic and evidentiary effectiveness. Conclusion . The results of the study showed the relationship of changes in the activity of cardiospecific auto-A T to cardiomyocyte proteins (Anti-cTnI, Anti ACTC1, Anti-M YH7B) in patients with cardiac pathologies, indicating not only systemic membrane disorders (membranopathies), but also serve as convincing evidence of direct chemical changes in cardiomyocytes. A correlation has also been established between cardiomarkers of necrosis and ischemia and autoimmune globulins Anti-cTnI, Anti ACTC1, Anti-MYH7B, that confirms diagnostic and practical value of this laboratory analysis.

INTRODUCTION: Type 1 diabetes is a chronic disease characterized by a selective loss of pancreatic ?-cells with a disproportionate recent increase at ages under 5-years old. Its etiology is multifactorial, to which immune factors contribute through pancreatic autoantibodies. Our main aim is to assess whether the type of pancreatic autoantibody influence the clinical symptoms, glycated hemoglobin and glycemia at diagnosis of type 1 diabetes in children diagnosed under ten-years of age. METHODS: Observational, retrospective and analytical study carried out with a total of 95 patients included. We compared two groups (aged ?60 months and >60 months) and each type of autoantibody (positive/negative) regarding demographic, immune, clinical and laboratory characteristics. The autoantibodies studied were islet cell autoantibodies (against cytoplasmic proteins in the ?-cell), antibodies to glutamic acid decarboxylase, anti-insulin and anti-zinc transporter 8. The impact of autoimmunity, glycated hemoglobin, gender and age on clinical and laboratory parameters of these children was analyzed. RESULTS: Children diagnosed over 60 months had a higher glycated hemoglobin value (p=0.005) and this laboratory parameter was the only one that showed an impact on the initial presentation as diabetic ketoacidosis (CI95%: OR=1.66;p=0.001). The value of glycemia at admission showed to be influenced negatively by age (?=--0.25;p=0.022) and positively by glycated hemoglobin (?=0.35;p=0.001). None of the autoantibodies evaluated seemed to interfere in the clinical and laboratory manifestations of type 1 diabetes. CONCLUSION: Demographic, clinical and laboratory characteristics showed no statistically significant differences between two groups of positive/negative pancreatic autoantibodies analyzed. It is crucial to develop further studies in the scope of autoimmunity that allow to structure potential immune phenotypes and assist in the discovery of new therapeutic targets.

Summary: Background: Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. Methods: Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n = 216) and MIS-C (n = 56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. Findings: ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P = 0·02) and anti-IL-22 (P = 0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P = 0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P = 0·02); and sCD25 (P = 0·009), angiopoietin-2 (P = 0·001), soluble IL-33-receptor (ST2, P = 0·01) and CXCL10 (P = 0·02) with ICU admission in MIS-C. Interpretation: Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. Funding: The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication.

Key Clinical Message Fetal bradycardia and congenital complete heart block could be the presentation of neonatal lupus. A high index of suspicion of this condition helps to identify an asymptomatic mother. Abstract Neonatal lupus erythematosus (NLE) is a rare acquired autoimmune disease of newborns due to placental transfer of Ro/SSA or La/SSB autoantibodies. Though cardiac, cutaneous, hematological, and hepatobiliary abnormalities are detected, cardiac defects cause significant morbidity and mortality. We report a case of complete congenital heart block due to NLE.

The identification of autoantigens remains a critical challenge for understanding and treating autoimmune diseases. Autoimmune polyendocrine syndrome type 1 (APS1), a rare monogenic form of autoimmunity, presents as widespread autoimmunity with T and B cell responses to multiple organs. Importantly, autoantibody discovery in APS1 can illuminate fundamental disease pathogenesis, and many of the antigens found in APS1 extend to more common autoimmune diseases. Here, we performed proteome-wide programmable phage-display (PhIP-Seq) on sera from a cohort of people with APS1 and discovered multiple common antibody targets. These novel APS1 autoantigens exhibit tissue-restricted expression, including expression in enteroendocrine cells, pineal gland, and dental enamel. Using detailed clinical phenotyping, we find novel associations between autoantibodies and organ-restricted autoimmunity, including a link between anti-KHDC3L autoantibodies and premature ovarian insufficiency, and between anti-RFX6 autoantibodies and diarrheal-type intestinal dysfunction. Our study highlights the utility of PhIP-Seq for extensively interrogating antigenic repertoires in human autoimmunity and the importance of antigen discovery for improved understanding of disease mechanisms.

Adult-onset polymyositis (PM) belongs to the idiopathic inflammatory myopathy (IIM) group and manifests with proximal muscle weakness, elevated muscle enzymes and positive myositis- specific antibodies. The subset of autoantibodies can indicate a higher risk for cancer association. An 82-year-old diabetic patient, with multiple cardio-vascular comorbidities, was hospitalized for muscle weakness of the upper girdle, dysphagia and dysphonia, accompanied by elevated serum muscle enzymes. Muscle biopsy showed an inflammatory infiltrate while immunological assays found positive ANA and anti-NXP2 antibodies. The diagnosis of PM was established, thus a screening for underlying neoplasia was required. Upper endoscopy visualized an area of ectopic mucosa in the esophagogastric junction and the biopsy confirmed a squamous cell carcinoma in situ. Patient had favorable muscle outcome under methylprednisolone pulse therapy. It is worth noting that polymyositis is more rarely associated with cancers as compared to dermatomyositis (DM). In conclusion, the type of antibodies identified in myositis can represent an alarm signal for oncologic screening, making possible an early diagnosis and efficient treatment of a hidden tumor.

Relevance. In conditions of ever-increasing volume of training loads, the frequency of cases of chronic physical overstrain (CPO) among athletes is increasing. It determines the importance of early diagnosis of the formed pathology of the cardiovascular system in order to prevent its further development. The aim of the study was to study the dynamics of autoantibodies to cardiomyocyte proteins using an experimental model of CPO and to determine the prospects of a laboratory method for the determination of autoantibodies for early diagnosis of pathomorphological changes in the heart. Materials and Methods. The study was conducted on male white rats. A treadmill was used to model CPO. In animals, the heart rate was measured, electrical phenomena in the heart were recorded. The content of hemoglobin and erythrocytes was determined in the blood. The level of cardiospecific autoantibodies (auto-AB) to troponin I, to alpha-actin 1, and to the heavy chain of beta-myosin 7B was measured. Heart mass was measured and histomorphological assessment of the state of cardiomyocytes was carried out. Results and Discussion. While modeling CPO, a decrease in body weight of the animals, the development of anemia, and cardiac hypertrophy were recorded. A decrease in body weight by more than 30 % was recorded from days 25 to 35 of the modeled CPO. A decrease in the number of erythrocytes in the blood was noted on day 25 with a peak fall on days 30-35. The mass of heart of animals in the dynamics of 0-15-35 days was 0.39±0.003; 0.41±0.001; 0.44±0.005 g/100 g, respectively. On day 25, sinus tachycardia was recorded in 2 % of the animals. On days 30 and 35, in 10 % of the studied rats, a violation of the processes of repolarization of the left ventricle by the type of subepicardial ischemia was recorded. On the 25th day, fibrosis of the perivascular region was visualized, passing into the interstitial field between the myofibrils. Reticulate structures of connective tissue fibers between cardiomyocytes were found. The period of 30-35 days was characterized by even greater severity of pathomorphological changes: myocardial hypertrophy, moderate myocardial dystrophy, interstitial and perivascular fibrosis. An increase in the number of detectable auto-ABs to cardiomyocyte proteins was noted on the 10th day of the experiment. A multiple increase in autoantibodies to cardiomyocyte proteins was recorded earlier than functional disorders in the heart and morphological changes in cardiomyocytes were detected. Conclusion. The laboratory method for determining auto-ABs to myocardial proteins can be the earliest of the complex methods for diagnosing disorders that are formed in the body in conditions of adaptation to intense and prolonged physical exertion.

Aim:The association between high levels of anti-thyroid antibodies and the extent of destruction of thyroid tissue is well documented. The aim of the present study was to analyze the relationship between anti-thyroid antibodies, thyroid hormones, and sonographic parenchymal changes.Methods:The study was designed as a case-control study. Four hundred and seventy-five patients with HT and 98 healthy subjects were included in the study. Serum levels of free thyroxine (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone, and anti-thyroid antibodies (anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies) were measured. The ultrasonographic results of the patients were also recorded.Results:Serum levels of anti-TPO and anti-Tg were significantly associated with hypoechogenicity, heterogeneity, and pseudonodulation (p

The review is devoted to the relationship between the pathogenetic mechanisms of coronavirus infection (COVID-19) and immunoinflammatory rheumatic diseases (IRD). The current knowledge on the pathogenesis of COVID-19 is summarized, including the mechanisms of coagulopathy, hyperproduction of pro-inflammatory cytokines, and antiphospholipid antibodies that are common with IRD. The presence and clinical significance of detection of various autoantibodies in COVID-19, which probably play a pathogenetic role in immune dysregulation, were analyzed. Based on the data of recent studies, risk factors and features of the severe course of infection in patients with IRD are considered.

Background: Depression is one of the significant problems in adults that accounts for up to five percent of cases worldwide.

Abstract Background The increasing incidence of breast cancer necessitates the need to explore alternate screening strategies that circumvent the setbacks of conventional techniques especially among population that report earlier age at diagnosis. Serum autoantibodies is one such potential area of interest. However, their ubiquitous presence across cancer types limits its applicability to any one specific type of cancer. This review was therefore carried out to explore and consolidate available evidence on autoantibodies for early detection of breast cancer and to identify those that demonstrated a higher sensitivity. Methods A diagnostic test accuracy (DTA) review was carried out to ascertain serum autoantibodies that could be used for early detection of breast cancer among women. All relevant articles that investigated the role of autoantibodies in early detection of breast cancer were included for the review. MEDLINE, Scopus, ProQuest, Ovid SP, and Cochrane Library were searched extensively for eligible studies. Quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. RevMan 5.3 was used for exploratory and MetaDTA 2019 for hierarchical analyses. The review helped identify the most frequently investigated autoantibodies and a meta-analysis further consolidated the findings. Results A total of 53 articles were included for the final analysis that reported over a 100 autoantibodies that were studied for early detection of breast cancer in women. P53, MUC1, HER2, HSP60, P16, Cyclin B1, and c-Myc were the most frequently investigated autoantibodies. Of these P53, MUC1, HER2, and HSP60 exhibited higher summary sensitivity measures. While the individual pooled sensitivity estimates ranged between 10 and 56%, the panel sensitivity values reported across studies were higher with an estimated range of 60–87%. Conclusion Findings from the review indicate a higher sensitivity for an autoantibody panel in comparison to individual assays. A panel comprising of P53, MUC1, HER2, and HSP60 autoantibodies has the potential to be investigated as an early detection biomarker for breast cancer.

Abstract Background Hepatitis C virus (HCV) infection is a serious public health concern due to its high prevalence and mortality rate. In chronic infection, HCV may induce autoimmune responses through the production of autoantibodies, including antinuclear antibodies (ANA). Methods We assessed the presence of ANA by indirect immunofluorescence using HEp-2 cells in 89 patients with chronic hepatitis C. We also collected data on epidemiological variables; clinical characteristics; and biochemical, hematological, molecular, and histopathological information from the patients to assess the impact of the presence of ANA in those patients. Results The prevalence of ANA in the patients was 20.2%, which was significantly higher than that found in healthy controls (2%). However, there was no association of this marker with epidemiological, clinical-laboratory, molecular or histopathological characteristics of hepatitis C, although a slightly higher prevalence of ANA was detected in women and in patients infected with subgenotype 1a. In a specific analysis, chronic HCV patients with the “rods and rings” cytoplasmic pattern had higher degrees of hepatic fibrosis than did ANA-negative patients. Conclusions The results confirm a greater predisposition to the presence of ANA in patients with HCV, which may be associated with a worse prognosis, especially in the presence of the “rods and rings” cytoplasmic pattern.

Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune inflammatory myositis with symmetrical proximal muscle weakness and a characteristic rash. Juvenile dermatomyositis is characterized by variable presentation and phenotypes. Detection of myositis autoantibodies is useful in improving JDM diagnosis and predicting the prognosis. In this literature review based on case series we analyze clinical and autoantibody phenotypes of JDM in four patients who were hospitalized in one regional center in Ukraine during the last 3 years and three of them presented in the time of the COVID-19 pandemic. The reviewed literature showed the last updates for the JDM diagnosis and the role of myositis autoantibodies in the prediction of disease course, systemic involvement, and malignancy risk. The presence of anti-synthetase syndrome in all presented patients, mainly due to anti-PL-7 autoantibodies, encourages further study with more patients and with detection of other myositis-specific autoantibodies to identify or refute certain regional features.

Summary: Background: Type 1 diabetes is a complex heterogenous autoimmune disease without therapeutic interventions available to prevent or reverse the disease. This study aimed to identify transcriptional changes associated with the disease progression in patients with recent-onset type 1 diabetes. Methods: Whole-blood samples were collected as part of the INNODIA study at baseline and 12 months after diagnosis of type 1 diabetes. We used linear mixed-effects modelling on RNA-seq data to identify genes associated with age, sex, or disease progression. Cell-type proportions were estimated from the RNA-seq data using computational deconvolution. Associations to clinical variables were estimated using Pearson's or point-biserial correlation for continuous and dichotomous variables, respectively, using only complete pairs of observations. Findings: We found that genes and pathways related to innate immunity were downregulated during the first year after diagnosis. Significant associations of the gene expression changes were found with ZnT8A autoantibody positivity. Rate of change in the expression of 16 genes between baseline and 12 months was found to predict the decline in C-peptide at 24 months. Interestingly and consistent with earlier reports, increased B cell levels and decreased neutrophil levels were associated with the rapid progression. Interpretation: There is considerable individual variation in the rate of progression from appearance of type 1 diabetes-specific autoantibodies to clinical disease. Patient stratification and prediction of disease progression can help in developing more personalised therapeutic strategies for different disease endotypes. Funding: A full list of funding bodies can be found under Acknowledgments.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare autoimmune condition associated with recombinant adenovirus (rAV)-based COVID-19 vaccines. It is thought to arise from autoantibodies targeting platelet factor 4 (aPF4), triggered by vaccine-induced inflammation and the formation of neo-antigenic complexes between PF4 and the rAV vector. To investigate the specific induction of aPF4 by rAV-based vaccines, we examined sera from rAV vaccine recipients (AZD1222, AD26.COV2.S) and messenger RNA (mRNA) based (mRNA-1273, BNT162b2) COVID-19 vaccine recipients. We compared the antibody fold change (FC) for aPF4 and for antiphospholipid antibodies (aPL) of rAV to mRNA vaccine recipients. We combined two biobanks of Dutch healthcare workers and matched rAV-vaccinated individuals to mRNA-vaccinated controls, based on age, sex and prior history of COVID-19 (AZD1222: 37, Ad26.COV2.S: 35, mRNA-1273: 47, BNT162b2: 26). We found no significant differences in aPF4 FCs after the first (0.99 vs. 1.08, mean difference (MD) = −0.11 (95% CI −0.23 to 0.057)) and second doses of AZD1222 (0.99 vs. 1.10, MD = −0.11 (95% CI −0.31 to 0.10)) and after a single dose of Ad26.COV2.S compared to mRNA-based vaccines (1.01 vs. 0.99, MD = 0.026 (95% CI −0.13 to 0.18)). The mean FCs for the aPL in rAV-based vaccine recipients were similar to those in mRNA-based vaccines. No correlation was observed between post-vaccination aPF4 levels and vaccine type (mean aPF difference −0.070 (95% CI −0.14 to 0.002) mRNA vs. rAV). In summary, our study indicates that rAV and mRNA-based COVID-19 vaccines do not substantially elevate aPF4 levels in healthy individuals.

The 80+ existing autoimmune disorders (ADs) affect billions with little prevention or treatment options, except for temporary symptomatic management, leading to enormous human suffering and a monumental financial burden. The autoantibodies formed in most ADs have been identified, allowing the development of novel anti-idiotypic antibodies to mute the autoantibodies using vaccines. Nucleoside vaccines have been successfully tested as antigen-specific immunotherapies (ASI), with mRNA technology offering multi-epitope targeting to mute multiple autoantibodies. This paper proposes using mRNA technology to produce anti-idiotypic antibodies with broad effectiveness in preventing and treating them. This paper delves into the state-of-the-art mRNA design strategies used to develop novel ASIs by selecting appropriate T cell and B cell epitopes to generate anti-idiotypic antibodies. The low cost and fast development of mRNA vaccines make this technology the most affordable for the global control of ADs.

The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously appreciated; ii) neutralizing autoantibodies to type I interferons (IFNs) could provide protection against type 1 diabetes in these patients (Meyer et al., 2016). We attempted to replicate these new findings using a similar experimental approach in an independent patient cohort, and found no evidence for either conclusion.

As the most common autoimmune thyroid disease, Hashimoto's thyroiditis (HT) is also the primary cause of hypothyroidism, leading to increased risk of mental diseases, and even myxedema and coma. However, there are few studies on clinical treatments for HT. Thyroid autoantibodies produced in serum due to autoimmune disorders, may be significantly involved in the diagnosis and prognosis of HT. Evidence has suggested that the controlling for the intake of nutrient elements (such as appropriate selenium supplementation and iodine intake) may improve thyroid function by notably reducing the thyroid autoantibody titer, indicating the treatment may be positive in treating HT. But the correlations of various nutritional factors with HT treatment are still controversial. We reviewed recent developments in the treatment of HT, then summarized the influence of controlling for the intake of various nutritional factors (such as selenium, iodine, iron and vitamin D) on the treatment of HT, and concluded that the controlling may help to reduce thyroid autoantibody titers, and improve the therapeutic effect, and may be a reference for clinical treatment of HT.

Myositis specific autoantibodies(MSA) are important for the diagnosis and classification of idiopathic inflammatory myopathy (IIM). It reveales that there is a close relationship between various types of MSA and unique clinical manifestations as well as pathological phenotypes. The titers of some autoantibodies are also correlated with the disease activity score and prognosis. Therefore, detection of MSA is helpful to the identification of the disease subtypes, personalized treatment selection and the judgement of prognosis in clinical practice. In future, more in-depth researches on MSA are needed to furtherly explore the pathogenic mechanism of the disease.

The discovery of novel autoantibodies in neurological disorders contributes to a better understanding of its pathogenesis, improves the accuracy of diagnosis, and leads to new treatment strategies. Advances in techniques for the screening and detection of autoantibodies have enabled the discovery of new antibodies in the central nervous system (CNS) and neuromuscular diseases. Cell-based assays using live or fixed cells overexpressing target antigens are widely used for autoantibody-based diagnosis in clinical practice. Common pathogenic autoantibodies are unknown in most patients with multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Novel pathogenic autoantibodies to aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) have been identified in neuromyelitis optica spectrum disorder and MOG antibody-associated disease, respectively. These diseases have clinical similarities to MS, but with the discovery of pathogenic autoantibodies, they are now recognized as distinct disease entities. Antibodies to paranodal membrane proteins such as neurofascin-155, contactin‑1, contactin‑associated protein‑1 in CIDP and muscle-specific kinase and low-density lipoprotein receptor–related protein 4 in myasthenia gravis were added to the profiles of autoantibodies in neurological disorders. Despite the relatively low frequency of seropositivity, autoantibody detection is currently essential for the clinical diagnosis of CNS and neuromuscular autoimmune disorders, and differential approaches to seropositive patients will contribute to more personalized medicine. We reviewed recent discoveries of autoantibodies and their clinical implications in CNS and neuromuscular disorders.

Abstract Acquired hemophilia A (AHA) is a potentially life‐threatening hemorrhagic disorder with many etiologies. We report the first case in the literature describing the association of AHA with adult‐onset Still's disease (AOSD).

Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) or deficient (C57BL/6lpr/lpr) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal Gdf15−/− C57BL/6 and lupus-prone C57BL/6lpr/lpr mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system.