Common Autoantibodies Research Articles

Autoimmune diseases, autoantibody status and silicosis in a cohort of 1238 workers from the artificial stone benchtop industry

ObjectivesAutoimmune disorders are multifactorial but occupational exposures have long been implicated, including respirable crystalline silica (RCS). A modern epidemic of silicosis is emerging internationally, associated with dry processing of engineered...

Management and outcomes of interstitial lung disease associated with anti-synthetase syndrome: A systematic literature review.

Anti-synthetase syndrome (ASS) is a chronic autoimmune condition, with interstitial lung disease (ILD) being a key feature. This systematic literature review (SLR; CRD42023416414) aimed to summarise treatments and outcomes of ILD associated with ASS (ASS-ILD). Databases were searched for articles discussing ASS-ILD management and outcomes, published 1946-September 2023.Screening and data-extraction were performed by two reviewers. Meta-analysis, using a random effects model, and paired t-tests, were undertaken where appropriate to evaluate post-treatment-change in Pulmonary Function Tests (PFT). Ten articles were included, comprising 514 patients: 67.8% female, mean age 52.4years (SD4.6). Baseline high-resolution computed tomography was documented in 447 patients (86.9%); the most common pattern was non-specific interstitial pneumonia (n = 220; 49.2%). The most common myositis-associated autoantibody was anti-Jo1 (48%) with 27.8% having associated anti-Ro52 antibodies.Pooled estimates, after meta-analysis, for baseline Forced Vital Capacity (FVC) was 60.8% predicted (SE 2.1), and Diffusion Capacity of Lungs for Carbon Monoxide (DLco) was 49.8% (SE 3.5). After one-year, pooled improvement in FVC was 14.1% from baseline (SE 3.1) and in DLco was 15.1% (SE 2.8). Paired t-test demonstrated significant overall improvement in FVC (p = 0.007) and DLco (p = 0.002).Patients receiving RTX had 12.2% improvement in FVC and 2.9% increase in DLco at one-year; for patients receiving CYC, there was 17% improvement and 6.3% increase, respectively. 28 deaths were reported. Our SLR, the first to summarise management and outcomes of ASS-ILD, found no conclusive difference between effectiveness of treatments. More robust trials are required to reduce morbidity and mortality resulting from ASS-ILD.

Clinical Performance of the Line Immunoassay and Digital Liquid Chip Method for Detecting Autoimmune Liver Disease Autoantibodies.

The identification of autoantibodies associated with autoimmune liver disease (ALD) is crucial for diagnosis and management. Various laboratory methods have been introduced to detect autoantibody profiles. However, the variable performance of these assays may create challenges for clinicians and patients. To investigate the concordance rates and diagnostic performance of 2 commercially available assays, line immunoassay (LIA) and digital liquid chip method (DLCM), in patients with ALD. A total of 291 serum samples were collected, consisting of 180 sera from patients with ALD and 111 sera from controls. The samples were detected through LIA and DLCM. The agreement and diagnostic performance of each assay were analyzed. There was substantial to almost perfect agreement among prevalent autoantibodies (anti-mitochondrial antibody M2, antibodies against gp210, Sp100, and Ro52). Nevertheless, the Cohen κ coefficient of some uncommon autoantibodies (anti-LKM-1, anti-LC-1, and anti-SLA/LP) between the 2 methods was not ideal. LIA showed slightly better sensitivity, accuracy, and negative predictive value, while DLCM exhibited slightly higher specificity and positive predictive value. LIA and DLCM demonstrated comparable performance for the detection of common ALD-related autoantibodies. LIA seemed to be more sensitive, while DLCM displayed more specificity. However, standardization of ALD autoantibody detection still faces challenges between these diverse detection systems. Comprehensive interlaboratory validation is essential to mitigate potential misunderstanding and confusion among patients and clinicians.

Doxycycline for the treatment of nodding syndrome: a randomised, placebo-controlled, phase 2 trial

Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment. In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913. Between Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. 6 weeks of doxycycline did not affect the concentration of autoantibodies to HNPs, seizure control, disease severity, or quality of life at the 24-month follow-up but substantially decreased Ov16 antibody concentrations; the median plasma signal-to-noise Ov16 ratio was 16·4 (95% CI 6·4-38·4), compared with 27·9 (8·2-65·8; p=0·033) for placebo. 14 (6%) participants died and, other than one traffic death, all deaths were seizure-related. Acute seizure-related hospitalisations (rate ratio [RR] 0·43 [95% CI 0·20-0·94], p=0·028) and deaths (RR 0·46 [0·24-0·89], p=0·028) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 on placebo (p=0·50), and 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) on placebo (p=0·039). Doxycycline was safe; there was no difference in the incidence of grade 3-5 adverse events across the two groups. Nodding syndrome is strongly associated with O volvulus and the pathogenesis is probably mediated through an O volvulus induced autoantibody response to multiple proteins. Although it did not reverse disease symptoms, doxycycline or another prophylactic antibiotic could be considered as adjunct therapy to antiseizure medication, as it might reduce fatal complications from acute seizures and status epilepticus induced by febrile infections. Medical Research Council (UK). For the Luo translation of the abstract see Supplementary Materials section.

Autoimmune nodopathy

AbstractAutoimmune nodopathy (AN) is characterized by the presence of autoantibodies targeting molecules essential for saltatory conduction in myelinated nerves. Clinical manifestations of AN show similarities with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), including progressive and symmetrical sensorimotor deficits with electrophysiological demyelinating features in nerve conduction studies. Although no common autoantibodies have yet been identified in CIDP, AN is characterized by autoantibodies that primarily target specific molecular complex structures represented by the Ranvier node and paranode. Furthermore, these autoantibodies, such as neurofascin‐155 (NF155), contactin‐1 (CNTN1), contactin‐related protein 1 (Caspr1), and the CNTN1/Caspr1 complex, are illustrative examples of such autoantibodies. They can disrupt the septal‐like junction of paranodes without triggering cellular immune responses. AN manifests uniquely with symptoms such as ataxia, tremors, and markedly high cerebrospinal fluid (CSF) protein levels, often accompanied by nerve root and cranial nerve hypertrophy. Notably, this condition is resistant to immunotherapies typically effective against CIDP, including intravenous immunoglobulin therapy (IVIg). Current evidence suggests that B‐cell depletion therapies, such as rituximab, could benefit AN treatment. Since it has been suggested that existing treatments for CIDP may be effective in cases of autoantibody positivity of subclasses other than IgG4, CIDP that is resistant to conventional therapy requires novel therapeutic strategies that take into account the possibility of IgG4 autoantibodies.

Clinical Features and Outcomes of Patients with Idiopathic Inflammatory Myositis-Associated Interstitial Lung Disease in Rural Appalachia: A Cross-Sectional Study.

Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders often complicated by interstitial lung disease (ILD). The clinical characteristics and outcomes of IIM-associated ILD have been reported variably, but the literature on rural populations is scarce. A retrospective cross-sectional study was conducted at a rural tertiary academic medical center. Twenty-nine patients met the final inclusion criteria. The primary outcome was to assess the disease state and immunological and radiographic features of IIM-associated ILD. Secondary outcomes included disease progression, ILD exacerbation, mortality rate, and factors associated with poor outcome. Dermatomyositis (n = 15, 51.72%) followed by polymyositis (n = 8, 27.58%) were predominant myopathies. The most common autoantibodies were anti-Jo1 antibodies (n = 11, 37.93%). Indeterminate usual interstitial pneumonitis (41.30%, n = 12) was the most common radiographic pattern followed by non-specific interstitial pneumonia (n = 5, 17.24%). ILD exacerbation (n = 14, 66.66%) and mortality rate (n = 6, 20.69%) were high. Albumin levels were significantly lower in patients who died. The clinical characteristics of patients with IIM-associated ILD in rural Appalachia exhibit notable distinctions, and outcomes are worse compared to other populations. Larger studies are needed to investigate other prognostics factors and longitudinal trends of clinical characteristics and outcomes of IIM-associated ILD in rural populations.

Extremely Early Appearance of Islet Autoantibodies in Genetically Susceptible Children

Objective. We studied the characteristics of children who developed islet autoantibodies by the age of 0.50 years and hypothesized that the appearance of extremely early islet autoimmunity differs between four birth cohorts within 1994–2019 according to the change in the incidence of Type 1 diabetes (T1D) in Finland. Methods. Data from Finnish children participating in the Type 1 Diabetes Prediction and Prevention (DIPP) study, or the Environmental Determinants of Diabetes in the Young (TEDDY) study were analyzed. These studies follow children with increased HLA-conferred risk for T1D with regular measurements of islet autoantibodies. Maternally transferred antibodies were excluded by comparing islet autoantibodies in cord serum, child’s first follow-up serum and the maternal serum. Results. Among 20,979 Finnish children at increased risk to T1D, 53 (0.25%) developed at least one islet autoantibody at the age of ≤0.50 years. During a mean follow-up of 8.1 years, 15.1% progressed to T1D (median age at diagnosis 2.0 years), 43.4% developed confirmed islet autoimmunity but no T1D, and 41.5% had only transient islet autoantibodies. IAA was the most common first-appearing autoantibody. Among progressors, age at diagnosis was 1.0–2.4 years in children with IAA-initiated autoimmunity and 4.5–16.1 years in ZnT8A-initiated autoimmunity. When comparing children developing autoantibodies either at the age of ≤0.50 years or 0.51–0.75 years, confirmed positivity during follow-up was more common in the older group (81.7% vs. 58.5%; p = 0.002 ). In four birth cohorts within 1994–2019 appearance of islet autoantibodies at the age of ≤0.50 years decreased towards the most recent birth cohorts ( p = 0.016 ). Conclusion. Islet autoimmunity by the age of 0.50 years was rare in genetically susceptible children and was typically initiated with IAA. Confirmed positivity was less common in children with autoantibodies at age ≤0.50 than at slightly older age. The secular decrease of islet autoimmunity before age 0.50 years was observed. This trial is registered with NCT03269084 and NCT00279318.

Identification of Autoantibodies Associated with Connective Tissue Disorders in Idiopathic Multicentric Castleman Disease

Background: Idiopathic multicentric Castleman disease (iMCD) is a rare, atypical lymphoproliferative disorder with significant morbidity and mortality and unknown etiology. While anti-interleukin-6 (IL-6) therapy with siltuximab is effective in 34-50% of iMCD patients, disease pathophysiology remains largely unknown. A fundamental question is whether iMCD is most appropriately considered an infectious disease caused by an as-yet-unknown pathogen, an autoimmune disease caused by autoantibodies, an autoinflammatory disease caused by germline mutations, or a neoplastic disease caused by somatic mutations in a clonal cell population. While limited evidence exists for each of these hypotheses, the pathogen hypothesis has been the most systematically evaluated to date. In this study, we quantified the levels of autoantibodies that may be involved in iMCD pathology. Methods: We constructed two custom bead-based protein arrays to screen serum samples for IgG autoantibodies from iMCD patients (n = 101) and healthy controls (HC, n = 30). The Connective Tissue Disease (CTD) array consisted of 52 antigens associated with traditional CTDs including in Scleroderma, Myositis/Overlap Syndromes, Systemic Lupus Erythematosus (SLE)/Sjögren's, GI/Endocrine, DNA-Associated, and Inflammation/Stress. The Anti-Cytokine Autoantibody (ACA) array included 38 cytokines, chemokines, and cell surface proteins. Serum samples came from the University of Pennsylvania (n = 38), University of Arkansas for Medical Sciences (n = 45), and Osaka University (Japan, n = 18). A “positive” autoantibody result in any sample was defined as greater than five standard deviations (SD) above the average mean fluorescent intensity (MFI) of the HC and at least 3,000 MFI. Fisher's exact tests were used to determine associations between autoantibody positivity and disease status. Results: To evaluate assay precision, we investigated anti-IL-6 antibodies given that a large portion (38%) of iMCD patients were on anti-IL-6 therapy. As expected, 40 iMCD samples were positive for anti-IL-6 antibodies, the most common autoantibody detected in iMCD subjects. IL-6 was then removed from further analyses. Next, we evaluated the proportion of CTD autoantibody positive iMCD patients. Overall, 46 (46%) iMCD subjects were positive for a CTD autoantibody compared to five (17%) in HCs (OR 4.1, P = 0.005) (Figure 1A). When investigating autoantibody prevalence in CTD subcategories, Myositis/Overlap Syndromes (OR 7.5, P = 0.026) and SLE/Sjögren's (OR 6.2, P = 0.073) autoantibodies trended higher in iMCD patients, but these associations did not survive multiple testing correction. The most common Myositis/Overlap Syndrome autoantibodies were anti-Mi2 (iMCD: 7/101 vs HC: 0/30), and anti-SRP54 (7/101 vs 0/30). The most common SLE/Sjögren's autoantibodies were anti-La/SSB (9/101 vs 0/30) and anti-Ro60 (5/101 vs 0/30). For the custom ACA array, there were significantly more ACA positive iMCD subjects (n = 40, 40%) than HC (n = 3, 10%; OR 5.8, P = 0.002) (Figure 1B). The most common ACAs in iMCD were anti-OSM (9/101 vs 0/30), anti-TNF (6/101 vs 0/30), anti-ITM2B (6/101 vs 0/30), and IFNe (5/101 vs 1/30). Conclusions: IgG autoantibodies associated with CTDs, such as anti-Mi2, anti-SRP54, anti-La, anti-Ro, and anti-Histone 3; and ACAs, such as anti-OSM, anti-TNF, and anti-ITM2B were common in iMCD patients. While autoantibodies suggest autoimmune involvement, the presence of autoantibodies does not directly implicate autoimmunity as a pathological mechanism. For example, Hodgkin's disease and other post-infectious etiologies can present with elevated autoantibodies. Although not surviving multiple hypothesis correction, myositis and SLE autoantibodies trended higher in iMCD patients. While most of these autoantibodies have not been reported, anti-Ro and and anti-La antibodies have been reported previously in iMCD case reports. The presence of anti-OSM is interesting, as OSM is a member of the IL-6 family. Two hypothesized mechanisms include that autoantibodies may be non-neutralizing leading to increased half-life and cytokine activity or autoantibodies are neutralizing and lack of negative feedback from OSM may lead to increased signaling via other IL-6-family cytokines. More research is needed to understand the role of these autoantibodies and, if pathogenic, whether iMCD should be considered an autoimmune disease.

Association between Thyroid Autoantibodies and Abnormal Thyroid Function and Structure of Thyroid Gland

Introduction: Antithyroperoxidase antibody (TPOAb), antithyroid receptor antibody (TRAb) and antithyroglobulin antibody (TgAb) are common thyroid autoantibodies in patients with autoimmune thyroid disease. Studies have demonstrated that the serum presence of thyroid autoantibodies is correlated with the presence of lymphocytic infiltration and the severity of histological thyroiditis. However, one or more of these antibodies are frequently detected in the general population. Abnormalities in thyroid function and structure are common in the population. Aim of the study: The aim of this study was to evaluate the association between thyroid autoantibodies and abnormalities in thyroid function and structure. Methods: This was a multi-center, cross-section, observational study and was conducted in the Department of Endocrinology of Ibn Sina Medical College Hospital, Dhaka, Bangladesh and Enam Medical College, Savar, Dhaka, Bangladesh during the period from September, 2022 to September, 2023. In our study we included 324 patients with thyroid dysfunction. The patients were selected consecutively attending tertiary care hospitals. The study participants provided demographic and clinical data. Thyroid function, thyroid ultrasonogram and serum concentration of TPOAb, TRAb, and TgAb were measured. Result: A total 324 patients were included in this study. Most of the study population were female (79%) and mean age were 37.0± 12.4 years. 58.6% belonged to the 21-40 age group. The mean BMI was found 22.0±4.5 kg/m2 in positive TRAb and 26.5±5.0 kg/m2 in negative TRAb. 229 (70.7%) were hypothyroid and 95 (29.3%) were hyperthyroid patients. Among the study population 211 (65.1%) patients were TPOAb, 112 (34.6%) were TgAb and 80 (24.7%) were TRAb positive. Among the TPOAb positive patients, 78.7% were hypothyroid and 21.3% were hyperthyroid. On the contrary, among the TRAb positive patients, 97.5% were hyperthyroid. Most (158) of the patients have normal ultrasonogram of thyroid. ..

The Role of Indirect Immunofluorescence (IIF) and Line Immunoassay (LIA) in the Diagnosis of Autoimmune Diseases and Their Clinical Correlation: An Observational Study From a Tertiary Care Center in Bihar.

Background and aim The presence of distinct sets of autoantigens and autoantibodies bestow these autoimmune diseases (ADs) with specific immune profiles or fingerprints, which has cleared the diagnostic dilemma associated with these ADs. This study was planned to collate and compare the reporting of indirect immunofluorescence (IIF) with line immunoassay (LIA) and their clinical correlations.This study was conducted to investigate the association between the reporting of anti-nuclear antibody (ANA) screening by IIF and ANA profile reporting by LIA. Additionally, it aimed to explore the association of ANA pattern detection by IIF with the detection of autoantibodies against nuclear antigens by LIA and the association of autoantibody detection by LIA with clinical diagnosis. Methodology A total of 98 samples from patients suspected of having ADs were subjected to both IIF and LIA, and results were correlated with clinical diagnosis. Results In the homogenous pattern noted by IIF, the clustered antigens identified by LIA included dsDNA, Nucleosome, Histone, and Mi-2. In the speckled pattern, the identified antigens were SS-A/Ro52, P0, SS-A/Ro60, SS-B/La, and U1-snRNP. On the other hand, the nucleolar pattern revealed antigens AMA M2, PCNA, and CENP-B. The centromere pattern was mostly associated with CENP-B. The speckled pattern was found to be most commonly associated with systemic lupus erythematosus (SLE). The most common autoantibody found in total ANA profile-positive samples was anti-U1-snRNP followed by anti-SS-A/Ro60 and anti-SS-B/La, and all three were found to be associated with SLE. Conclusions SLE was the most common AD identified in our study samples, with the speckled pattern being the most common pattern on IIF and anti-U1-snRNP being the most common ANA identified by LIA. The fluorescence pattern of IIF predicts the presence of specific antibodies. LIA should be reserved for IIF-positive but dubious casesand whose signs and symptoms are nebulous and do not match the disease dictated by IIF.

B-078 Prevelance of Autoimmune Factors in Patients with Seizures of Unknown Etiology in Western China

Abstract Objective To delineate the features of autoantibody in patients with seizure of unknown etiology in Western China and to analyze other potential risk factors of an epileptic seizure. Methods From January 2017 to June 2022, 639 patients with unexplained seizure were assessed retrospectively. Neuronal autoantibodies were assessed in 471 individuals, including 12 common neural-specific autoantibodies, antibodies against four common pathogens associated with central nervous system infections, or neurophagocytosis, and two thyroid-related autoantibodies. Results Sixty-nine patients were positive for neural-specific autoantibodies in CSF and serum. Among the patients, 32 (46.38%) expressed NMDAR-Ab, 14 (20.29%) expressed GABABR-Ab, 10 (14.49%) expressed LGI1-Ab, 7 (10.14%) expressed GFAP-Ab, 3 (4.34%) expressed Yo-Ab, 2 (2.90%) expressed CASP2-Ab, and 1 (1.45%) expressed Hu-Ab. Compared to patients with non-autoimmune epileptic seizure, the positive rates of thyroid-related antibody expression and the neurophagocytosis pathogen levels of HSV-IgG and T. gondii-IgG were significantly different in patients with autoimmune epileptic seizure. Conclusion This study elucidated the antibody status of autoimmune epilepsy in western China, allowing for better identification and diagnosis of autoimmune epilepsy in the future.

Autoimmune Atrial Fibrillation.

Atrial fibrillation (AF) is by far the most common cardiac arrhythmia. In about 3% of individuals, AF develops as a primary disorder without any identifiable trigger (idiopathic or historically termed lone AF). In line with the emerging field of autoantibody-related cardiac arrhythmias, the objective of this study was to explore whether autoantibodies targeting cardiac ion channels can underlie unexplained AF. Peptide microarray was used to screen patient samples for autoantibodies. We compared patients with unexplained AF (n=37 pre-existent AF; n=14 incident AF on follow-up) to age- and sex-matched controls (n=37). Electrophysiological properties of the identified autoantibody were then tested in vitro with the patch clamp technique and in vivo with an experimental mouse model of immunization. A common autoantibody response against Kir3.4 protein was detected in patients with AF and even before the development of clinically apparent AF. Kir3.4 protein forms a heterotetramer that underlies the cardiac acetylcholine-activated inwardly rectifying K+ current, IKACh. Functional studies on human induced pluripotent stem cell-derived atrial cardiomyocytes showed that anti-Kir3.4 IgG purified from patients with AF shortened action potentials and enhanced the constitutive form of IKACh, both key mediators of AF. To establish a causal relationship, we developed a mouse model of Kir3.4 autoimmunity. Electrophysiological study in Kir3.4-immunized mice showed that Kir3.4 autoantibodies significantly reduced atrial effective refractory period and predisposed animals to a 2.8-fold increased susceptibility to AF. To our knowledge, this is the first report of an autoimmune pathogenesis of AF with direct evidence of Kir3.4 autoantibody-mediated AF.

The Predictive Value of Autoantibodies in Determining Autoimmune Hepatitis (AIH) Severity

Background: The presence of autoantibodies is a prerequisite for the diagnosis of autoimmune hepatitis (AIH). However, most autoantibodies are not disease-specific, and serological overlap between AIH and other chronic liver diseases is common. Since the prognostic parameters of AIH are limited, this study aimed to investigate the relationship between histopathological findings on liver biopsy with different types of autoantibodies associated with AIH and how autoantibodies can predict the severity and extent of disease. Methods: The present study was performed on 30 patients with a definite diagnosis of AIH according to the International Autoimmune Hepatitis Group (IAIHG) criteria. Pediatric AIH patients underwent liver tissue examinations at the time of diagnosis at accession, which confirmed characteristic histological changes. AIH-related serologic major and minor autoantibodies were measured using indirect immunofluorescence assays and ELISA kit (EUROIMMUN, Germany), respectively, and were compared within all patients, and the results were recorded. Finally, the obtained data were analyzed using SPSS V25 software. Results: Out of 30 patients, 17 (56.66%) were female, and the age range of patients was 17-11 years (8.46±6.95). Anti-nuclear antibody (ANA) (73.3%), smooth muscle antibody (SMA)-anti-smooth muscle actin antibody (ASMA) (70%), perinuclear anti-neutrophilic cytoplasmic antibodies (p-ANCA) (63%), and liver kidney microsomal (LKM) (43.3%) were the most common autoantibodies found in children with AIH. There was a significant relation between the severity of histological findings and the presence of LKM antibodies (P&lt;0.05). The highest sensitivity for predicting severe AIH based on histopathological findings was ANA autoantibody positivity and the presence of at least two primary autoantibodies (LKM and SMA-ASMA). On the other hand, positive LKM antibodies had the highest specificity and positive predictive value (PPV) in AIH severity prediction. Conclusion: The results of the present study suggested that there might be a significant correlation between the presence of primary LKM autoantibodies and biopsy results, so it can possibly act as an accurate autoantibody for predicting the severity of AIH, while other AIH-related autoantibodies did not seem to have a significant correlation with biochemical and histological findings.

The significance of dense fine speckled pattern in antinuclear antibody-associated rheumatic disease and coexisting autoantibodies: A propensity score-matched cohort study.

To investigate the relationship between the prevalence of antinuclear antibody (ANA) -associated rheumatic diseases (AARD) and the presence of dense fine speckled (DFS) and homogeneous patterns in ANA tests. This retrospective study enrolled adult patients with either a DFS or homogeneous pattern in their ANA test. A mixed pattern was defined as the presence of more than one pattern reported in the test. The presence of anti-DFS70 antibodies and other common autoantibodies were detected using EUROLINE ANA Profile 23. A 1:2 propensity score matching was applied to control for demographic and other interfering factors. A total of 59 patients with a DFS pattern were enrolled and compared with a matched homogeneous group. The DFS group had a significantly lower prevalence of AARD (3.4% vs. 16.9%, p = .008) and the subgroup with anti-DFS70 antibodies showed an even lower prevalence (2% vs. 20%, p = .002). Among the 33 patients with monospecific anti-DFS70 antibodies, five had a mixed pattern, and all patients with common autoantibodies had an isolated DFS pattern. The findings of this study suggest that patients with a DFS pattern in their ANA test may have a lower prevalence of AARD compared with those with a homogeneous pattern. However, an isolated DFS pattern in ANA testing does not necessarily indicate the presence of monospecific anti-DFS70 antibodies or AARD. Confirmatory testing for the monospecific anti-DFS70 antibody is mandatory to exclude AARD.

Atrophic Gastritis and Autoimmunity: Results from a Prospective, Multicenter Study.

Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this "new" type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning with chronic atrophic gastritis (CAG), precedes GC. To test the possible existence of autoimmunity in patients with CAG, we aimed to analyze the prevalence of several autoantibodies in patients with CAG as compared to control patients. Sera of 355 patients included in our previous prospective, multicenter study were tested for 19 autoantibodies (anti-nuclear antibodies, ANA, anti-parietal cell antibody, APCA, anti-intrinsic factor antibody, AIFA, and 16 myositis-associated antibodies). The results were compared between CAG patients (n = 154), including autoimmune gastritis patients (AIG, n = 45), non-autoimmune gastritis patients (NAIG, n = 109), and control patients (n = 201). ANA positivity was significantly higher in AIG than in NAIG or control patients (46.7%, 29%, and 27%, respectively, p = 0.04). Female gender was positively associated with ANA positivity (OR 0.51 (0.31-0.81), p = 0.005), while age and H. pylori infection status were not. Myositis-associated antibodies were found in 8.9% of AIG, 5.5% of NAIG, and 4.4% of control patients, without significant differences among the groups (p = 0.8). Higher APCA and AIFA positivity was confirmed in AIG, and was not associated with H. pylori infection, age, or gender in the multivariate analysis. ANA antibodies are significantly more prevalent in AIG than in control patients, but the clinical significance of this finding remains to be established. H. pylori infection does not affect autoantibody seropositivity (ANA, APCA, AIFA). The positivity of myositis-associated antibodies is not increased in patients with CAG as compared to control patients. Overall, our results do not support an overrepresentation of common autoantibodies in patients with CAG.

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Autoantibody Profile and Lung HRCT Scan in Systemic Sclerosis with Restrictive Lung 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.

Metabolic phenotyping of pilomotor seizures in autoimmune encephalitis.

Ictal piloerection (IP) is an uncommon symptom in focal epilepsy and is associated with autoimmune encephalitis (AE). However, the networks involved in AE-associated IP are still unclear. To have a better understanding of IP underlying mechanisms, the current study investigated whole-brain metabolic networks for the analysis of AE-associated IP. Patients with AE and IP diagnosed at our Institute between 2018 and 2022 were selected. We then investigated the brain regions associated with AE-associated IP using positron emission tomography (PET). Anatomometabolic changes (interictal 18 F fluorodeoxyglucose PET) in AE patients with IP were compared with those of AE patients of similar age without IP (p-voxel <0.001, uncorrected). Sixteen patients showed significant IP. The overall IP prevalence was 4.09% of patients with AE and 12.9% of patients with limbic encephalitis. The most common autoantibodies were against LGI1 (68.8%) followed by GAD65 (6.3%), NMDA (6.3%), GABAb (6.3%), CASPR2 (6.3%), and antibodies recognizing both GAD65 and mGLUR5 (6.3%). Most patients responded well to immunotherapy. Analysis of the imaging results at the voxel level showed that patients with IP had hypermetabolic changes in the right inferior temporal gyrus, suggesting involvement of this brain region in IP. Our findings indicate that IP as an uncommon AE-associated manifestations should be recognized. We observed that the metabolic pattern of IP was conspicuous in the right inferior temporal gyrus.

Glycine receptor autoantibody binding to the extracellular domain is independent from receptor glycosylation.

Glycine receptor (GlyR) autoantibodies are associated with stiff-person syndrome and the life-threatening progressive encephalomyelitis with rigidity and myoclonus in children and adults. Patient histories show variability in symptoms and responses to therapeutic treatments. A better understanding of the autoantibody pathology is required to develop improved therapeutic strategies. So far, the underlying molecular pathomechanisms include enhanced receptor internalization and direct receptor blocking altering GlyR function. A common epitope of autoantibodies against the GlyRα1 has been previously defined to residues 1A-33G at the N-terminus of the mature GlyR extracellular domain. However, if other autoantibody binding sites exist or additional GlyR residues are involved in autoantibody binding is yet unknown. The present study investigates the importance of receptor glycosylation for binding of anti-GlyR autoantibodies. The glycine receptor α1 harbors only one glycosylation site at the amino acid residue asparagine 38 localized in close vicinity to the identified common autoantibody epitope. First, non-glycosylated GlyRs were characterized using protein biochemical approaches as well as electrophysiological recordings and molecular modeling. Molecular modeling of non-glycosylated GlyRα1 did not show major structural alterations. Moreover, non-glycosylation of the GlyRα1N38Q did not prevent the receptor from surface expression. At the functional level, the non-glycosylated GlyR demonstrated reduced glycine potency, but patient GlyR autoantibodies still bound to the surface-expressed non-glycosylated receptor protein in living cells. Efficient adsorption of GlyR autoantibodies from patient samples was possible by binding to native glycosylated and non-glycosylated GlyRα1 expressed in living not fixed transfected HEK293 cells. Binding of patient-derived GlyR autoantibodies to the non-glycosylated GlyRα1 offered the possibility to use purified non-glycosylated GlyR extracellular domain constructs coated on ELISA plates and use them as a fast screening readout for the presence of GlyR autoantibodies in patient serum samples. Following successful adsorption of patient autoantibodies by GlyR ECDs, binding to primary motoneurons and transfected cells was absent. Our results indicate that the glycine receptor autoantibody binding is independent of the receptor's glycosylation state. Purified non-glycosylated receptor domains harbouring the autoantibody epitope thus provide, an additional reliable experimental tool besides binding to native receptors in cell-based assays for detection of autoantibody presence in patient sera.

Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation.

Takayasu arteritis (TAK) is a type of large-vessel vasculitis that predominantly affects young females. The precise pathomechanism of TAK is still under investigation. In TAK, the vasa vasorum is considered to be the initial inflammatory site. Disruption of the vasa vasorum induces the entry of inflammatory cells into the vascular wall of large vessels between the media and adventitia, and infiltrated cells damage the vascular components, eventually leading to stenosis or dilatation of the affected arteries. In addition, T cells are considered key players in TAK, and myeloid cells function as effector cells. Although the roles of B cells in TAK are poorly understood, recent evidence supports their contribution to the pathogenicity of TAK. Particularly, two autoantibodies have been identified in TAK through investigation of anti-endothelial cell antibodies, and they could be involved in the maintenance of vascular inflammation. Furthermore, one of the autoantibodies, anti-endothelial protein C receptor, was shown to be present in ulcerative colitis (UC), which is genetically and clinically associated with TAK. Similar autoantibodies in inflammatory diseases with different target organs indicate a common underlying pathophysiology of these diseases, which could be characterized by the aberrant activation of B cells. This review discusses recent understanding of the pathomechanisms of TAK and UC, with a focus on the involvement of B cells and autoantibodies. The close association of UC with TAK further suggests a common etiology, and the importance of the intestinal microbiota, including dysbiosis, is also becoming known in TAK. Investigation of such common factors among TAK and UC would improve understanding of the interplay between gut and vascular inflammation, which is a new concept for developing vascular inflammation through the gut-vessel connection.