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This paper describes the development of an enzyme-linked immunosorbent assay (ELISA) for the detection and quantitation of autoantibodies against the nuclear protein Scl-70. The isolation of Scl-70 from rat livers and the conditions for the ELISA are described. Compared with the already established double diffusion in gel for detection of anti-Scl-70 antibodies this ELISA has advantages.

Background: The aim of this study was to investigate the serum levels of anti-myelin basic protein (anti-MBP), anti-myelin oligodentrocyte glycoprotein (anti-MOG), myelin-associated glycoprotein (MAG), high-sensitivity C-reactive protein (hs-CRP), cerebral dopamine neurotrophic factor (CDNF), cerebellin-1, and reelin and their relationships with clinical severity and irritability behaviours in children with attention deficit (AD) hyperactivity disorder (ADHD) and typically developing (TD) healthy controls., Methods: In this study, 141 children with ADHD between the ages of 8 and 14 years who were medication-free and 135 TD healthy controls were included. The serum levels of anti-MBP, anti-MOG, MAG, CDNF, hs-CRP, cerebellin, and reelin were measured using enzyme-linked immunosorbent assay kits. The Turgay Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-based Screening and Evaluation Scale for Attention Deficit and Disruptive Behavior Disorders-Parent Form (TDSM-IV-O) and the affective reactivity index (ARI) scale were used to assess clinical severity and irritability behaviours in the children., Results: The MAG, CDNF, hs-CRP, reelin, and cerebellin levels were significantly higher in the ADHD group than in the control group, but no significant differences in anti-MBP and anti-MOG levels were found between the groups. Compared with the controls, the patients with ADHD showed significantly higher scores on the ARI self- and parent-report scales. The reelin, hs-CRP, and MAG levels were significantly associated with the TDSM-IV-O AD scores, AD and oppositional defiant (OD) disorder scores and hyperactivity, and OD and conduct disorder scores, respectively. Hs-CRP was significantly associated with anti-MBP and cerebellin levels. In an analysis of covariance, the results were unchanged even after controlling for potential confounders such as age, body mass index, and sex., Conclusion: This study demonstrates that MAG, CDNF, hs-CRP, reelin, and cerebellin levels may play a potential role in the pathogenesis of ADHD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Low vitamin D levels are commonly observed in autoimmune diseases, suggesting a potential role in disease pathogenesis. The presence of anti-vitamin D antibodies may contribute to these deficiencies and influence autoimmune processes., Objective: To review and analyze studies investigating the occurrence of anti-vitamin D antibodies in autoimmune diseases., Results: Three studies, comprising a total of 345 patients, were reviewed. The autoimmune conditions included systemic lupus erythematosus (SLE), scleroderma (SSc), primary antiphospholipid antibody syndrome (pAPS), and pemphigus vulgaris (PV). Patient mean ages ranged from 26.8 to 31 years, with the proportion of female participants ranging from 87 % to 96 %. The duration of disease varied between 6.3 and 12.3 years. Serum vitamin D levels ranged from 11.71 ± 7.21 to 28.4 ± 9.6 ng/mL, with 57.1 % to 82.1 % of patients presenting vitamin D deficiency. The prevalence of anti-vitamin D antibodies was reported as follows: 87 % in SSc, 11 % in PV, 4 % to 6.1 % in SLE, and 3.5 % in pAPS. Associations with other disease markers were also noted: in SLE, anti-vitamin D antibodies were associated with anti-dsDNA antibodies; while in SSc, their presence was linked to the disease itself., Conclusion: Anti-vitamin D antibodies were identified in 3.5 % to 87 % of patients with SLE, SSc, pAPS, and PV. These antibodies are associated either with the autoimmune condition itself or with other autoantibodies, suggesting their potential role in disease mechanisms and progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is one of the most common antibody-mediated CNS disorders. Optimal diagnostic and prognostic biomarkers remain unclear. Our aim was to clarify these biomarkers and therapeutic outcomes internationally. We reviewed articles from 2007 to 2022 and identified 194 unique cohorts encompassing 4699 paediatric and adult patients from 31 countries. Where phenotypes were specified, the most common initial presentation overall was optic neuritis (ON; paediatric 34 %; adults 60 %), during which 71 % had papilloedema on fundoscopy. The most common phenotype at latest follow-up was relapsing ON (20 %). Only 47 % of patients with 6-24 months of follow-up exhibited a relapsing course, while this proportion was much higher (72 %) when follow-up was extended beyond 5 years. Despite a similar relapse rate, the time to first relapse was much shorter in paediatric than adult patients (6 vs 17 months). Adult MRI-Brain scans performed at onset were more frequently normal than in paediatric patients (50 % vs 27 %). Abnormal MRI scans showing involvement of deep grey matter, cortico-subcortical, periventricular lesions, leptomeningeal enhancement, H-shaped spinal cord lesions, and bilateral optic nerve abnormalities were more common in paediatric patients compared to adults. Conversely, adults demonstrated higher frequencies of eccentric spinal cord lesions and intraorbital involvement. CSF analysis demonstrated intrathecally restricted oligoclonal bands in 12 %, elevated protein in 35 %, and pleocytosis in 54 %. Peripapillary retinal nerve fibre layer (pRNFL) thickness, measured acutely, frequently demonstrated swelling (weighted-median 145 μm; normal 85-110). Most cohorts demonstrated notable pRNFL atrophy at latest follow-up (weighted-median 67 μm). pRNFL thickness was significantly lower when measured at or after six months following ON onset, compared to measurements taken within the first six months following ON onset (p < 0.001). Therapeutic and outcome data was available for 3031 patients with a weighted-median disease duration of 32 months. Acute immunotherapy was initiated in 97 %, and maintenance immunotherapy in 64 %, with considerable regional variation. Expanded Disability Status Scale (EDSS) scores and visual acuities improved from nadir to latest follow-up in most patients. A negative correlation was noted between follow-up pRNFL thickness and latest follow-up visual acuity (r = -0.56). Based on this unprecedented global aggregation of MOGAD patients, we reveal a higher proportion of relapsing patients than previously recognised. While commonly used measures like EDSS show significant recovery, they underestimate visual disability following optic neuritis, the most frequent clinical presentation. Our findings suggest that RNFL thickness, especially when measured at least 6 months post-ON, may serve as a more sensitive biomarker for long-term visual impairment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sudarshini Ramanathan reports financial support was provided by NHMRC Investigator Grant GNT2008339. Sudarshini Ramanathan reports a relationship with National Health and Medical Research Council that includes: funding grants. Funding BT receives a University of Sydney postgraduate scholarship and a stipend from CIA Ramanathan's Royal Australasian College of Physicians Research Establishment Fellowship. FB has received research funding from NSW Health, MS Australia, the NHMRC (Australia), the Medical Research Future Fund (Australia), The MOG Project (Apollo Grant) and Novartis. RCD has received research funding from the Star Scientific Foundation, The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia, the Petre Foundation and the NHMRC (Australia; Investigator Grant). SR has received research funding from the National Health and Medical Research Council (NHMRC, Australia), the Petre Foundation, the Brain Foundation, the Royal Australasian College of Physicians, and the University of Sydney. She is supported by an NHMRC Investigator Grant (GNT2008339). Competing Interests BT was on an advisory board for Merck. FB was on an advisory board for Novartis and Merck, and has been an invited speaker for Biogen, Novartis and Limbic Neurology. She is on the medical advisory board (non-remunerated positions) of The MOG Project and the Sumaira Foundation. RCD received honoraria from Biogen Idec as an invited speaker, and is on the IDMC for a Roche RCT in paediatric MS. He is on the medical advisory board (non-remunerated position) of The MOG Project. SR serves as a consultant on an advisory board for UCB and Limbic Neurology and has been an invited speaker for educational/research sessions coordinated by Biogen, Alexion, Novartis, Excemed and Limbic Neurology. She is on the medical advisory board (non-remunerated positions) of The MOG Project and the Sumaira Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Dyslipidemia is described in several autoimmune conditions. Lipoprotein lipase (LPL) is responsible for triglyceride breakdown. Anti-LPL antibodies have been described., Objective: To review articles on anti-LPL antibodies in autoimmune and non-autoimmune diseases., Results: Twenty-two articles were found: 9 case reports and 13 observational studies. In 5 of 9 case reports, hypertriglyceridemia normalized after immunosuppressive treatment. The observational studies showed the prevalence and associations of anti-LPL antibodies: systemic lupus erythematosus, found in 37.8 % to 71 % of patients and associated with nephritis, disease activity, and the presence of anti-dsDNA antibodies. In myositis, the prevalence ranged from 4 % to 43 % without any reported association. In scleroderma, they were found in 35 % to 42 % and associated with skin and lung fibrosis, heart involvement, and the presence of anti-topoisomerase-1 antibodies. In Sjögren's syndrome and rheumatoid arthritis, they were found in a minority of individuals. They were absent in Behçet's disease, antiphospholipid antibody syndrome, juvenile idiopathic arthritis, juvenile dermatomyositis, and Takayasu arteritis. Three studies were conducted on dyslipidemic patients without autoimmune conditions, and in one of them, anti-LPL antibodies were associated with necrosis in atherosclerotic plaques., Conclusion: Anti-LPL antibodies were detected in several autoimmune and non-autoimmune diseases, mainly connective tissue diseases, and were associated with increased triglyceride levels. These antibodies may contribute to the accelerated atherogenesis seen in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anti-contactin associated protein receptor 2 (CASPR2) encephalitis is a severe autoimmune encephalitis with a variable clinical phenotype including behavioral abnormalities, cognitive decline, epileptic seizures, peripheral nerve hyperexcitability and neuropathic pain. The detailed mechanisms of how CASPR2 autoantibodies lead to synaptic dysfunction and clinical symptoms are largely unknown. Aiming for analyses from the molecular to the clinical level, we isolated antibody-secreting cells from the cerebrospinal fluid of two patients with CASPR2 encephalitis. From these we cloned four anti-CASPR2 human monoclonal autoantibodies (mAbs) with strong binding to brain and peripheral nerves. All were highly hypermutated and mainly of the IgG4 subclass. Mutagenesis studies determined selective binding to the discoidin domain of CASPR2. Surface plasmon resonance revealed affinities with dissociation constants K D in the pico- to nanomolar range. CASPR2 mAbs interrupted the interaction of CASPR2 with its binding partner contactin 2 in vitro and were internalized after binding to CASPR2-expressing cells. Electrophysiological recordings of rat hippocampal slices after stereotactic injection of CASPR2 mAbs showed characteristic afterpotentials following electrical stimulation. In vivo experiments with intracerebroventricular administration of human CASPR2 mAbs into mice and rats showed EEG-recorded brain hyperexcitability but no spontaneous recurrent seizures. Behavioral assessment of infused mice showed a subtle clinical phenotype, mainly affecting sociability. Mouse brain MRI exhibited markedly reduced resting-state functional connectivity without short-term structural changes. Together, the experimental data support the direct pathogenicity of CASPR2 autoantibodies. The minimally invasive EEG and MRI techniques applied here may serve as novel objective, quantifiable tools for improved animal models, in particular for subtle neuropsychiatric phenotypes or repeated measurements., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Toxicological and epidemiological studies have shown that environmental endocrine disruptors interfere with hormonal homeostasis. However, there is limited research on the effects of mixed exposure to nonpersistent endocrine disruptors on thyroid hormones and the factors (e.g., presence status of thyroid autoantibodies or nutritional status of organismal iodine) that may influence this association., Methods: Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2011-2012. Relationships between single pollutants and thyroid hormone and thyroid autoantibody levels were assessed using generalized linear (GLM) and restricted cubic spline (RCS) regression models. Weighted quantile sum regression (WQS), group-weighted quantile sum regression (GWQS), quantile-based g-computation (qgcomp), and adaptive elasticity network (AENET) were applied to assess the mixed exposure effect. Next, subgroup analyses were performed on the basis of the urinary iodine concentration or thyroid autoantibody status to assess the modifying role of urinary iodine and thyroid autoantibodies., Results: A total of 2385 study participants were included in this study. Both the single-pollutant model and the multipollutant mixed model revealed that parabens and bis(2-ethylhexyl) phthalate (DEHP) metabolites were significantly and negatively associated with serum thyroxine (T4) levels. However, no associations were found between the target pollutants and thyroid autoantibodies (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)). In addition, this study revealed that urinary iodine or thyroid autoantibody status altered the associations of some of the target pollutants with thyroid hormones. WQS and qgcomp analyses, revealed that the associations of mixed pollutants with hormones differed depending on the urinary iodine or antibody status, especially T4 and thyroid-stimulating hormone (TSH)., Conclusion: Significant associations were found between phenols, parabens, and phthalates and serum thyroid hormone levels, with parabens and DEHP metabolites playing major roles. Urinary iodine and thyroid autoantibody status act as modifiers between environmental endocrine-disrupting pollutants and thyroid hormones., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Classification criteria of autoimmune rheumatic diseases are an important means to define homogenous groups of patients that can be compared across studies for clinical trials and research purposes. The measurement of autoantibodies is a relevant aspect in the definition of classification criteria, with a significant weight in the scores necessary to classify patients with autoimmune rheumatic diseases. The impact of autoantibodies has gradually increased over the years, contributing to the evolution and improvement of the classification criteria. However, these criteria often do not take into consideration how autoantibodies are measured, i.e. differences in diagnostic accuracy of the methods. This is a critical point especially when obsolete analytical methods that are no longer used in many clinical laboratories are taken into consideration. In this review we have critically examined assays and methods for the determination of autoantibodies that are (or could be) included among the classification criteria of autoimmune rheumatic diseases in light of more recent evidence and technology evolution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The contributions of anti-Topoisomerase 1 (Top1) autoantibodies to the pathophysiology of diffuse cutaneous systemic sclerosis (dcSSc), the most aggressive scleroderma subtype, are unknown. Top1 catalyzes DNA relaxation and unwinding in cell nuclei, a site previously considered inaccessible to antibodies. The discovery of autoantibodies in systemic lupus erythematosus that penetrate nuclei and inhibit DNA repair raised the possibility that nuclear-penetrating autoantibodies contribute to mechanisms of autoimmunity. Here we show that an anti-Top1 autoantibody produced by a single B cell clone from a patient with dcSSc penetrates live cells and localizes into nuclei. Functionally, the autoantibody inhibits formation of the Top1 cleavage complex necessary for DNA nicking, which distinguishes it from cytotoxic camptothecin Top1 inhibitors used in cancer therapy that trap the cleavage complex rather than preventing its formation. Discovery of a patient-derived cell-penetrating scleroderma anti-Top1 autoantibody that inhibits Top1 cleavage complex formation supports the hypothesis that anti-Top1 autoantibodies contribute to cellular dysfunction in dcSSc and offers a valuable antibody reagent resource for future studies on anti-Top1 autoantibody contributions to scleroderma pathophysiology., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: James E. Hansen, MD reports financial support was provided by Patrys Ltd. James E. Hansen, MD reports a relationship with Patrys Ltd that includes: consulting or advisory, equity or stocks, funding grants, and non-financial support. James E. Hansen, MD has patents licensed to Patrys Ltd. James E. Hansen, MD has patent pending to unlicensed. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The ZnT8 autoantibody is used to independently diagnose type 1 diabetes (T1D) and as a prediction factor in high-risk populations. This is the first report in Taiwan on the prevalence, diagnostic utility, and clinical characteristics of zinc transporter 8 autoantibody (ZnT8A) in children with T1D., Methods: We performed a retrospective analysis of 268 children (130 boys, 138 girls) newly diagnosed with T1D at three hospitals in North Taiwan from February 1994 to August 2021., Results: ZnT8A was detected in 117 patients (43.7 %). The combined diagnostic rate of the four antibodies, including glutamic acid decarboxylase autoantibody (GADA), islet antigen 2 autoantibody (IA2A), insulin autoantibody (IAA), and ZnT8A, can reach 86.19 % while that of the original three antibodies is 84.3 %. IA2A (64.9 %) showed the highest positive rate, followed by GADA (64.2 %), ZnT8A (43.7 %), and IAA (22.0 %). Of the 268 patients, five (1.9 %) were only ZnT8A + . All antibodies were positive in 19 (7.1 %) people, whereas 37 others (13.8 %) had all antibodies negative. ZnT8A has the strongest relationship with IA2A. 5 patients had ZnT8A positive only. 5/(37 + 5) (about 12 %) T1D patients were diagnosed by ZnT8A testing., Conclusions: ZnT8A testing can diagnose up to 12 % more patients with T1D along with three other antibodies. Furthermore, since the ZnT8A titer decreased over time, it should be tested within six months of onset in Taiwanese patients with T1D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Thyroid-stimulating hormone receptor autoantibodies (TRAbs) play a crucial role as pathogenic antibodies in both the diagnosis and management of Graves' disease (GD). GD, an autoimmune disease resulting from a combination of genetic and environmental factors, is the most common cause of hyperthyroidism. With advancements in technology for TRAb detection and the availability of automated commercial kits, TRAb has become an essential clinical laboratory marker for the diagnosis of GD, as well as extra-thyroidal manifestations like Graves' ophthalmopathy (GO). This article provides a comprehensive review of TRAb, encompassing its clinical assays along with its significance in the clinical setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antibodies against glutamic acid decarboxylase (anti-GAD) are a valuable diagnostic tool to detect severe autoimmune conditions as type 1 diabetes mellitus (T1DM) and anti-GAD related neurological disorders, having the latter more often anti-GAD concentrations in serum multiple times higher than in the former. Automated immunoassays, either with ELISA or chemiluminescent technology, are validated for diagnostic use in serum with analytical ranges suitable for T1DM diagnosis. In a patient presenting with a suspected autoimmune ataxia, anti-GAD testing on an automated chemiluminescent immunoassay (CLIA) resulted in slightly abnormal concentrations in serum (39.2 KIU/L) and very high concentrations in CSF (>280 KIU/L), thus prompting to proceed to serum dilutions to exclude a false negative result and a misdiagnosis. Different dilutions of serum resulted in nonlinear concentrations with endpoint result of 276,500 KIU/L at dilution 1:1000. CSF dilution was instead linear with endpoint result of 4050 KIU/L. In this case report we found that anti-GAD testing in CSF was essential to establish the clinical diagnosis and to suspect hook-effect in serum due to the excess of autoantibodies in this severe autoimmune condition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort., Methods: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719)., Findings: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I 2 : 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60])., Interpretation: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amelie Leurs reports a relationship with CSL Vifor that includes: travel reimbursement. Dr. Amelie Leurs reports a relationship with NOVARTIS that includes: board membership. Prof David Launay reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with Biocryst Pharmaceuticals, Inc. that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with CSL Behring LLC that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with GSK that includes: funding grants. Prof David Launay reports a relationship with Octapharma that includes: funding grants. Prof David Launay reports a relationship with Pfizer Inc. that includes: funding grants. Dr. Luc Dauchet reports a relationship with FEDER ECRIN that includes: funding grants. Dr. Luc Dauchet reports a relationship with ADEM French environment agency that includes: funding grants. Prof Vincent Sobanski reports equipment, drugs, or supplies was provided by Euroimmun. Prof Vincent Sobanski reports equipment, drugs, or supplies was provided by D-Tek. Prof Vincent Sobanski reports financial support was provided by Lille University Hospital. Prof Vincent Sobanski reports a relationship with Grifols Inc. that includes: consulting or advisory and funding grants. Prof Vincent Sobanski reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory. Prof Vincent Sobanski reports a relationship with Ultragenyx Pharmaceutical Inc. that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Autoantibodies are important laboratory markers to support diagnosis of autoimmune diseases. Interpretation of autoantibodies is classically done in a dichotomous way (positive versus negative). Yet, interpretation of autoantibody test results can be improved by reporting likelihood ratios. Likelihood ratios convey information on how much more/less likely a test result is in individuals with the disease compared to individuals without the disease. It incorporates information on the antibody level (the higher the antibody level, the higher the association with the disease), which is helpful for (differential) diagnosis. Likelihood ratios are unit-independent and allow users to harmonize test result interpretation. When the likelihood ratio is combined with information on the pre-test probability, post-test probability can be appraised. In this review, the applicability of likelihood ratio in autoimmune diagnostics will be reviewed from the perspective of the clinician, the laboratory professional and the in vitro diagnostic industry., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xavier Bossuyt reports a relationship with Thermo Fisher Scientific Inc. that includes: speaking and lecture fees. Xavier Bossuyt reports a relationship with Werfen that includes: consulting or advisory and speaking and lecture fees. Kevin Deane reports a relationship with Werfen that includes: consulting or advisory. Kevin Deane reports a relationship with Thermo Fisher Scientific Inc. that includes: consulting or advisory. Lieve Van Hoovels reports a relationship with Thermo Fisher Scientific Inc. that includes: speaking and lecture fees. Veena Joy reports a relationship with Thermo Fisher Scientific Inc. that includes: employment. Nina Olschowka reports a relationship with Thermo Fisher Scientific Inc. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Autoantibodies directed against the GluA3 subunit (anti-GluA3 hIgGs) of AMPA receptors have been identified in 20%-25% of patients with frontotemporal lobar degeneration (FTLD). Data from patients and in vitro/ex vivo pre-clinical studies indicate that anti-GluA3 hIgGs negatively affect glutamatergic neurotransmission. However, whether and how the chronic presence of anti-GluA3 hIgGs triggers synaptic dysfunctions and the appearance of FTLD-related neuropathological and behavioural signature has not been clarified yet. To address this question, we developed and characterized a pre-clinical mouse model of passive immunization with anti-GluA3 hIgGs purified from patients. In parallel, we clinically compared FTLD patients who were positive for anti-GluA3 hIgGs to negative ones. Clinical data showed that the presence of anti-GluA3 hIgGs defined a subgroup of patients with distinct clinical features. In the preclinical model, anti-GluA3 hIgGs administration led to accumulation of phospho-tau in the postsynaptic fraction and dendritic spine loss in the prefrontal cortex. Remarkably, the preclinical model exhibited behavioural disturbances that mostly reflected the deficits proper of patients positive for anti-GluA3 hIgGs. Of note, anti-GluA3 hIgGs-mediated alterations were rescued in the animal model by enhancing glutamatergic neurotransmission with a positive allosteric modulator of AMPA receptors. Overall, our study clarified the contribution of anti-GluA3 autoantibodies to central nervous system symptoms and pathology and identified a specific subgroup of FTLD patients. Our findings will be instrumental in the development of a therapeutic personalised medicine strategy for patients positive for anti-GluA3 hIgGs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Anti-dsDNA autoantibodies are listed as one of the classification criteria for systemic lupus erythematosus (SLE) and are relatively effective indicators for monitoring disease activity and treatment response. Therefore, clinicians rely on them to diagnose and adjust medication and treatment strategies for SLE patients. However, the use of anti-dsDNA antibodies is not free from controversy. Part of this controversy stems from the fact that anti-dsDNA antibodies are found in several disorders, besides SLE. In addition to this, anti-dsDNA antibodies are a heterogeneous group of antibodies, and their determination still lacks proper standardization. Moreover, anti-dsDNA testing specificity and diagnostic performance change depending on the population under study. These and other issues result in inconsistency and encumber the clinical use of anti-dsDNA antibodies. A panel of medical laboratory and clinical experts on SLE discussed such issues based on their clinical experience in a first meeting, establishing a series of recommendations. The proceedings of this first meeting, plus an exhaustive review of the literature, were used to compose a paper draft. The panel subsequently discussed and refined this draft in a second meeting, the result of which is this paper. This document is relevant to clinical laboratories as it guides to improving diagnosis and monitoring of SLE. Simultaneously, it will help laboratories compile more informative reports, not limited to a mere number. It is also relevant to clinical doctors who wish to better understand laboratory methods so that they can do a more efficient, better-aimed laboratory test ordering., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ricardo Rojo reports financial support was provided by Thermo Fisher Scientific. Jaime Calvo Alen reports financial support was provided by. Alvaro Prada reports financial support was provided by Thermo Fisher Scientific. Santiago Valor reports financial support was provided by Thermo Fisher Scientific. Garbine Roy reports financial support was provided by Thermo Fisher Scientific. Marcos Lopez-Hoyos reports financial support was provided by Thermo Fisher Scientific. Ricard Cervera reports financial support was provided by Thermo Fisher Scientific. Paloma Sanchez Mateos reports financial support was provided by Thermo Fisher Scientific. Aurora Jurado Roger reports financial support was provided by Thermo Fisher Scientific. Jaime Calvo Alen reports a relationship with Abbvie Spain, S.L.U. that includes: consulting or advisory. Jaime Calvo Alen reports a relationship with AstraZeneca that includes: consulting or advisory. Jaime Calvo Alen reports a relationship with Biogen that includes: consulting or advisory. Jaime Calvo Alen reports a relationship with Eli Lilly and Company that includes: consulting or advisory. Jaime Calvo Alen reports a relationship with GSK that includes: consulting or advisory. Jaime Calvo Alen reports a relationship with Janssen Pharmaceuticals Inc. that includes: consulting or advisory. Jaime Calvo Alen reports a relationship with Novartis that includes: consulting or advisory. Jaime Calvo Alen reports a relationship with Thermo Fisher Scientific that includes: consulting or advisory. Ricard Cervera reports a relationship with AstraZeneca that includes: consulting or advisory. Ricard Cervera reports a relationship with CellGenTech, Inc. that includes: consulting or advisory. Ricard Cervera reports a relationship with Eli Lilly and Company that includes: consulting or advisory. Ricard Cervera reports a relationship with GSK that includes: consulting or advisory. Ricard Cervera reports a relationship with Janssen Pharmaceuticals Inc. that includes: consulting or advisory. Ricard Cervera reports a relationship with Laboratorios Rubio SA that includes: consulting or advisory. Ricard Cervera reports a relationship with Thermo Fisher Scientific that includes: consulting or advisory. Marcos Lopez-Hoyos reports a relationship with Thermo Fisher Scientific that includes: consulting or advisory. Aurora Jurado Roger reports a relationship with Thermo Fisher Scientific that includes: consulting or advisory. Co-author member of Autoimmunity Reviews editorial board. Ricard Cervera. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Joint pain is one of the most debilitating symptoms of rheumatoid arthritis (RA) and patients frequently rate improvements in pain management as their priority. RA is hallmarked by the presence of anti-modified protein autoantibodies (AMPA) against post-translationally modified citrullinated, carbamylated and acetylated proteins. It has been suggested that autoantibody-mediated processes represent distinct mechanisms contributing to pain in RA. In this study, we investigated the pronociceptive properties of monoclonal AMPA 1325:01B09 (B09 mAb) derived from the plasma cell of an RA patient. We found that B09 mAb induces pain-like behavior in mice that is not associated with any visual, histological or transcriptional signs of inflammation in the joints, and not alleviated by non-steroidal anti-inflammatory drugs (NSAIDs). Instead, we found that B09 mAb is retained in dorsal root ganglia (DRG) and alters the expression of several satellite glia cell (SGC), neuron and macrophage-related factors in DRGs. Using mice that lack activating FcγRs, we uncovered that FcγRs are critical for the development of B09-induced pain-like behavior, and partially drive the transcriptional changes in the DRGs. Finally, we observed that B09 mAb binds SGC in vitro and in combination with external stimuli like ATP enhances transcriptional changes and protein release of pronociceptive factors from SGCs. We propose that certain RA antibodies bind epitopes in the DRG, here on SGCs, form immune complexes and activate resident macrophages via FcγR cross-linking. Our work supports the growing notion that autoantibodies can alter nociceptor signaling via mechanisms that are at large independent of local inflammatory processes in the joint., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Decreased autophagic flux in cardiomyocytes is an important mechanism by which the β 1 -adrenoreceptor (β 1 -AR) autoantibody (β 1 -AA) induces heart failure. A previous study found that β 1 -AA imparts its biological effects via the β 1 -AR/Gs/AC/cAMP/PKA canonical signaling pathway, but PKA inhibition does not completely reverse β 1 -AA-induced reduction in autophagy in myocardial tissues, suggesting that other signaling molecules participate in this process. This study confirmed that Epac1 upregulation is indeed involved β 1 -AA-induced decreased cardiomyocyte autophagy through CE3F4 pretreatment, Epac1 siRNA transfection, western blot and immunofluorescence methods. On this basis, we constructed β 1 -AR and β 2 -AR knockout mice, and used receptor knockout mice, β 1 -AR selective blocker (atenolol), and the β 2 -AR/Gi-biased agonist ICI 118551 to show that β 1 -AA upregulated Epac1 expression through β 1 -AR and β 2 -AR to inhibit autophagy, and biased activation of β 2 -AR/Gi signaling downregulated myocardial Epac1 expression to reverse β 1 -AA-induced myocardial autophagy inhibition. This study aimed to test the hypothesis that Epac1 acts as another effector downstream of cAMP on β 1 -AA-induced reduction in cardiomyocyte autophagy, and β 1 -AA upregulates myocardial Epac1 expression through β 1 -AR and β 2 -AR, and biased activation of the β 2 -AR/Gi signaling pathway can reverse β 1 -AA-induced myocardial autophagy inhibition. This study provides new ideas and therapeutic targets for the prevention and treatment of cardiovascular diseases related to dysregulated autophagy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: We investigated the association of serum anti-carbamylated protein (anti-CarP) antibodies with disease activity and bone loss in rheumatoid arthritis (RA)., Methods: The serum anti-CarP antibody concentrations of RA and non-RA patients and healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and then compared. The diagnostic value of anti-CarP antibodies in RA was determined by the receiver operating characteristic curve. Patients with RA and bone erosions were evaluated using ultrasound examinations. Ultrasonography was performed using a semiquantitative scale. The serum receptor activator of nuclear factor Κ-Β ligand (RANKL) concentrations were measured by ELISA to focus on bone loss., Results: Peripheral serum anti-CarP antibody concentrations in patients with RA were significantly higher than those in patients without RA and in healthy controls and were positively correlated with disease activity. Anti-CarP antibody concentrations were significantly increased in patients with anti-CCP-positive RA. Positive correlation were found between anti-CarP and RANKL. Increased serum anti-CarP antibodies in women with postmenopausal osteoporosis (OP)., Conclusions: Anti-CarP antibodies are associated with RA disease activity and may play an important role in bone loss associated with RA. The concentration of anti-CarP antibodies may be beneficial in the early diagnosis of RA, thus supporting its potential as a novel disease biomarker., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Immunofluorescence is a basic method for detection of autoantibodies in serum. It is used as screening for people with symptoms suggesting autoimmune process and disease. Antinuclear antibodies (ANA) assay detecting antibodies against nuclear proteins used commonly for diagnosis of systemic autoimmune disease, although antibodies against cytoplasmic components and mitotic structures are usable in clinic. The majority of ANA nuclear patterns have been comprehensively studied with increasing data. However, the cytoplasmic and mitotic patterns are underestimated and still require further assessment. In this review the clinical associations and significance of uncommon types of autoantibodies are presented and discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Anti-mitochondrial antibody (AMA) positivity is not always associated with primary biliary cholangitis (PBC). We aimed to determine the additional value of anti-sp100 or anti-gp210 antibody in AMA-positive patients for PBC., Methods: Patients (n = 190) and healthy donors (n = 50) were evaluated for AMA, anti-gp210 and anti-sp100 antibodies by ELISA. Antibody frequencies in cohorts and performance characteristics in some patients categorized as 'definitive-', 'probable-', and 'no PBC' were determined following review of their charts., Results: Of the patients (n = 190), 38.4% were AMA-positive (n = 73) and 61.6% AMA-negative (n = 117). Frequency of anti-sp100 or anti-gp210 antibody was 17.8%, 2.6%, and 0% in AMA-positive, AMA-negative and healthy controls, respectively. Clinical data was available for 63 of 73 AMA-positive patients with 28.6%, 22.2%, and 49.2% categorized as definite, probable, and no PBC, respectively. Patients with definite PBC had higher mean levels of AMA and frequencies of sp100 or gp210 antibody compared to other groups. Sensitivities were low (anti-sp100: 18.8% and anti-gp210: 16.7%) with specificities above 98.0% for both., Conclusion: AMA-positive patients positive for anti-sp100 or anti-gp210 antibody were more likely to have a diagnosis of definite or probable PBC than those with AMA alone. Use of all tests is likely to improve characterization of patients at-risk for PBC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To elucidate the clinical characteristics of Japanese pediatric patients with acquired demyelinating diseases (ADS), positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG), we conducted a nation-wide survey., Methods: Information about pediatric patients under 18 years old with ADS was solicited with surveys sent to 323 facilities. In an initial survey, we asked whether the center had any patients with ADS, and the MOG-IgG serostatus of the patients. In a follow-up survey, we requested more precise information on patients with ADS., Results: Initial survey: 263 replies providing information on 175 patients were received. MOG-IgG were examined in 78 patients and 54 of those (69%) were positive for MOG-IgG. Follow-up survey: The characteristic involvement was optic neuritis, with visual disturbance and optic pain as characteristic symptoms. The relapse rate was 44% in patients positive for MOG-IgG, which was higher than that in seronegative patients (38%). For acute phase treatments, corticosteroid (CS), plasma exchange, and intravenous immunoglobulin (IVIG) were useful. To prevent relapse, CS, intermittent IVIG, immunosuppressants, and monoclonal antibodies were useful, but the efficacies of disease modifying drugs were uncertain. Sequelae such as visual disturbance, cognitive impairment, motor dysfunction, and epilepsy were observed in 11% of patients with MOG-IgG., Conclusions: MOG antibody-associated diseases were found to be common among pediatric ADS patients. Since a variety of sequelae were observed in these patients, it is important to identify the appropriate treatment to ensure the best outcome. The presence of the MOG autoantibody should be taken into consideration as part of the diagnostic criteria for pediatric ADS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objectives: Clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis (DM) characterized by low-grade or absent muscle inflammation but frequent and rapidly progressive interstitial lung disease (RP-ILD) and skin ulcers with anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibodies. Basic leucine zipper transcription factor ATF-like 2 (BATF2) is thought to function as an inhibitor of tumours and inflammation. Here, we aimed to investigate the roles of BATF2 in Th cell differentiation of CADM with an anti-MDA5 autoantibody (anti-MDA5 + CADM)., Methods: Naive CD4 + T cells from human peripheral blood mononuclear cells (PBMCs) of healthy controls (HCs) were isolated and then cultured with IL-12, TGF-β or TGF-β plus IL-6 following anti-CD3 and anti-CD28 stimulations. The expression of BATF2 was measured by real-time PCR. The percentages of Th1, Th17 and Treg CD4 + T cells were detected by flow cytometry. BATF2 knockdown of CD4 + T cells was performed using small interfering RNAs (siRNAs)., Results: The expression of BATF2 in PBMCs was higher in anti-MDA5 + CADM patients than in healthy controls. The BATF2 mRNA expression was increased under Th1 and Treg polarization but decreased under Th17 polarization. Th17 cell activation-associated genes were possibly increased while Th1 and Treg cell differentiation-associated genes were inhibited by posttranscriptional gene silencing of BATF2 in CD4 + T cells., Conclusions: BATF2 promoted Th1 and Treg cell differentiation but suppressed Th17 cell activation in anti-MDA5 + CADM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The anti-citrillinated protein antibody (ACPA) plays an important role in early diagnosis of rheumatoid arthritis (RA), and is usually detected by using cyclic citrullinated peptide (CCP) as antigen. The ACPA against CCP test is usually performed utilizing enzyme-linked immunosorbent assay (ELISA), but the ELISA is expensive and time-consuming. Here, latex particle-enhanced turbidimetric immunoassay (LTIA) based on CCP-immobilized latex bead was proposed for fast measurements of ACPA of RA patients. CCP-immobilized latex bead was fabricated through three methods, including direct coupling, overall coupling and layer by layer coupling. According to the optimized experiments, layer-by-layer coupling was the best method with advantages of time-saving, simple operation and good repeatability. In addition, a spacer arm of appropriate length between latex beads and CCP could avoid stereoscopic obstacles and make ACPA closer to CCP. The CCP-immobilized latex bead based on layer by layer coupling (CCP-LB-LLC) was used for assembling the homemade kit, which was applied in fast measurements of ACPA through LTIA. The homemade kit possessed a low limit of detection (0.2 U/mL) and an acceptable the batch-to-batch reproducibility. In addition, the homemade kit can be stored at 4 °C for at least one month. When used to detect 20 clinical samples, the results of homemade kit were consistent with commercial ELISA. Furthermore, LTIA based on the homemade kit was simpler and cheaper than ELISA. These results demonstrated that the homemade kit could be useful for diagnosis of RA patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Anti-nuclear antibodies (ANA) are frequently detected in patients with psoriasis (Ps) and psoriatic arthritis (PsA), but their target autoantigens remain unknown. We assessed antibody (ab) reactivity against 23 known nuclear antigens in patients with Ps and PsA and assess the effects of secukinumab (anti-IL17A) treatment on ANA levels. A total of 201 patients, 101 with Ps and 100 with PsA, and 50 ANA-negative healthy controls (HCs) were tested for ANAs by a line immunoassay testing reactivity to 23 nuclear antigens. Ab reactivity to at least 1 antigen was found in 20.4% psoriatic disease patients (25.7% Ps and 15% PsA) compared to 8% HCs (p = ns), the most frequent being against dense fine speckled 70 (DFS70) (6.5%). In Ps and PsA patients with secukinumab-induced remission, anti-DFS70 and other antigen-specific autoantibodies were diminished over time. No decline was noted for IgG abs against antigens from pathogens such as cytomegalovirus, Epstein-Barr virus and Helicobacter pylori. Autoantibody decrease was associated with significant reduction of plasmablasts, follicular B and follicular T cells. In conclusion, one third of antigen-specific ANA patients with psoriatic disease recognize DFS70. Secukinumab decreases nuclear antigen autoreactivity, plasmablasts, follicular B and follicular T cells, highlighting a new mechanism of its action., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Wolfgang Meyer and Thomas Scheper are employees of Euroiimmun., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Non-HLA antibody responses following solid organ transplantation have become increasingly emphasised, with several large clinical series suggesting that such responses contribute to late graft failure. Many of the responses described recognise both recipient and donor moieties of the target antigen and thus represent auto-, rather than allo-immunity. Within this rapidly evolving field, many questions remain unanswered: what triggers the response; how innate and adaptive humoral autoimmunity integrate; and most pressingly, how autoimmunity contributes to graft damage and its relationship to other effector mechanisms of graft rejection. This review summarises recent clinical and experimental studies of humoral autoimmunity in transplant rejection, and considers some of the answers to these questions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Multiple Sclerosis (MS) is a chronic inflammatory disorder in the central nervous system for which biomarkers for diagnosis still remain unknown. One potential biomarker is the myelin basic protein. Here, a nanoimmunosensor based on atomic force spectroscopy (AFS) successfully detected autoantibodies against the MBP 85-99 peptide from myelin basic protein. The nanoimmunosensor consisted of an atomic force microscope tip functionalization with MBP 85-99 peptide, which was made to interact with a mica surface coated either with a layer of anti-MBP 85-99 (positive control) or samples of cerebrospinal fluid (CSF) from five multiple sclerosis (MS) patients at different stages of the disease and five non-MS subjects. The adhesion forces obtained from AFS pointed to a high concentration of anti-MBP 85-99 for the two patients at early stages of relapsing-remitting multiple sclerosis (RRMS), which were indistinguishable from the positive control. In contrast, considerably lower adhesion forces were measured for all the other eight subjects, including three MS patients with longer history of the disease and under treatment, without episodes of acute MS activity. We have also shown that the average adhesion force between MBP 85-99 and anti-MBP 85-99 is compatible with the value estimated using steered molecular dynamics. Though further tests will be required with a larger cohort of patients, the present results indicate that the nanoimmunosensor may be a simple tool to detect early-stage MS patients and be useful to understand the molecular mechanisms behind MS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To determine whether anti-Ro52 antibodies are associated with ILD in pSS., Methods: Retrospective study based on the presence or absence of anti-Ro52 antibodies in patients with pSS. Patients underwent chest HRCT at the time of diagnosis or during follow-up., Results: Sixty-eight patients were included. Two groups were defined by the presence (n = 31) or absence (n = 37) of anti-Ro52 antibodies. ILD was significantly higher in the presence of anti-Ro52 (41.9%, n = 13) versus in the anti-Ro52-negative group (16.2%, n = 6; p = 0.019). Multivariate analysis adjusted for anti-SSA/Ro60, anti-SSB antibodies and rheumatoid factor status confirmed that anti-Ro52 antibodies positivity is a predictive factor for ILD (p = 0.01). Nonspecific interstitial pneumonia was the most common pattern of ILD (31.6%). The majority of patients were diagnosed with pSS simultaneously to ILD (52.6%). In the anti-Ro52-negative group, no patients develop ILD after 5 years of follow-up., Conclusion: In pSS, the risk of developing ILD is higher in the presence of anti-Ro52 antibodies. In patients with pSS and anti-Ro52 antibodies, a clinical screening and pulmonary functional tests with DLCO is necessary during the follow-up and should comprise chest HRCT if there is a decline in the DLCO or clinical symptoms or inspiratory crackles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Bioluminescent solid-phase sandwich-type microassay was developed to detect multiple sclerosis (MS)-associated autoantibodies in human sera. The assay is based on two different 2'-F-Py RNA aptamers against the target autoantibodies as biospecific elements, and Ca 2+ -regulated photoprotein obelin as a reporter. The paper describes elaboration of the assay and its application to 91 serum samples from patients with clinically definite MS and 86 ones from individuals healthy in terms of MS. Based on the receiver-operator curve (ROC) analysis, the chosen threshold value as clinical decision limit offers sensitivity of 63.7% and specificity of 94.2%. The area under the ROC curve (AUC) value of 0.87 shows a good difference between the groups under investigation. The likelihood ratio of 10.97 proves the diagnostic value of the assay and its potential as one of the laboratory MS-tests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease characterized by a hemolytic anemia caused by autoantibodies against red blood cells (RBCs). These autoantibodies are routinely detected via the direct antiglobulin test (DAT). As expected, the DAT score correlates with the presence of clinical symptoms, but this correlation is far from perfect. Regularly, strongly positive DAT scores are encountered with no sign of hemolysis, while severe hemolysis can be seen even in patients with a negative DAT score. Apparently, the mere amount of antibody is not the sole predictor of disease. In this paper, we review the current literature on aspects of both the autoantibodies and the patients' clearance system that together determine the clinical significance of an anti-RBC autoantibody, ranging from antibody isotype to antibody Fc-glycosylation to alternative clearance mechanisms. From this, the ensemble of tests is inferred that in our view best assesses the main determinants for pathogenicity of autoantibodies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

At the 12th International Workshop on Autoantibodies and Autoimmunity (IWAA), organized in August 2014 in Sao Paulo, Brazil, more than 300 autoimmunologists gathered to discuss the status of many novel autoantibodies in clinical practice, and to envisage additional value of autoantibodies in terms of prediction, prognosis and prevention of autoimmune diseases. Two separate workshops were dedicated to standardization and harmonization of autoantibody testing and nomenclature: International Autoantibody Standardization (IAS) and International Consensus on ANA Patterns (ICAP). It was apparent to all in attendance that the discovery and elucidation of novel autoantibodies did not slow down, but that multiple challenges lay ahead of us in order to apply these discoveries to effective and efficient clinical practice. Importantly, this requires optimal bidirectional communication between clinicians and laboratory specialists, as well as close collaboration with the diagnostic industry. This paper is a report on the 12th IWAA in combination with a review of the recent developments in the field of autoantibodies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Several case reports, small case series, and original research papers have recently suggested that the action of certain auto-antibodies related to connective tissue diseases may be responsible for significant cardiac rhythm disturbances in adults. The relationship between anti-Ro/SSA antibodies and congenital complete atrioventricular block is well recognized in the fetal heart. Herein we review the emerging evidences of the link to increased levels of anti-Ro/SSA antibodies with rhythm disorders of unknown origin in the adult. Confirmation of this distinct etiology may eventually be the basis for new therapies., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

The relationship between depression and immunity has been widely discussed. Cytokines, such as TNF-α, play an important role in immune system; these cytokines interact with virtually every pathophysiologic domain relevant to depression, including neurotransmitter metabolism, neuroendocrine function, and synaptic plasticity. Antibodies have also been implicated in the pathophysiology of depression. The association between decreased serotonin levels and excessive glutamatergic activity forms the first biochemical basis for cytokine-induced depression. Cytokines and antibodies (anti-ribosomal-P and anti-N-methyl-D-aspartate receptor antibodies) are deeply related to pathogenesis of neurodevelopmental disorders, especially depression. Tumor necrosis factor alpha (TNF-α) may underlie the mechanism of depression by an activation of the hypothalamo-pituitary-adrenocortical (HPA) axis, an activation of neuronal serotonin transporters and the stimulation of the indoleamine 2,3-dioxygenase which leads to tryptophan depletion. In the last 20 years since the initial reports of neural-immune interactions in depression, studies have shown a clear association between activation of the immune system mediated by proinflammatory cytokines. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. To date, there are only few studies that investigated the relationship between depression and proinflammatory cytokines in patients with autoimmune diseases. Although an associative link between neuroinflammation and mood disorders is widely accepted, further studies are necessary to establish the cause-effect relationship. In this paper, we review the role of cytokines, focusing on TNF-α and antibodies in the depression and hypothesize how TNF-α may underlie and mediate the inflammatory process depression in patients with autoimmune disease., (Copyright © 2014. Published by Elsevier B.V.)

Despite the availability of effective treatments, Sarcoptes scabiei remains a major health problem in the pig industry. Unsuccessful control of the disease is often due to the lack of reliable detection methods, with current tests relying on skin scrapings and crude antigen ELISAs. A previous analysis of antigens in pig skin scrapings reported that anti-transferrin antibodies were present in S. scabiei infected animals and that this finding might be considered as a useful diagnostic tool. This paper confirms IgG autoantibodies against transferrin, including the first report of IgM autoantibodies, in both naturally and experimentally infected pigs using ELISA and dot blot assays. Autoantibodies were also detected in pigs to ferritin and to a lesser extent lactoferrin. Immunoblotting confirmed the presence of IgG and IgM autoantibodies in mange positive pigs, as well as IgM antibodies to transferrin and albumin in mange negative pigs. These findings suggest the presence of natural autoantibodies to transferrin and albumin in pigs. The development of the IgG autoimmune response may either be a host mechanism for limiting iron to the mite via antibody mediated clearance, the result of host exposure to mite iron-binding homologues or because of a mite-induced antigenic change to host transferrin. Further investigation into the formation of these autoantibodies may provide insights into the importance of iron in scabies infections and the development and perseverance of S. scabiei infections in pigs. The specificity and sensitivity of the anti-transferrin response reinforces its potential in the diagnosis of scabies in pigs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Anti-mitochondrial autoantibodies (AMA) are specific markers of primary biliary liver cirrhosis (PBC), a cholestatic autoimmune disease which is characterised by a progressive destruction of the biliary epithelial cells followed by fibrosis, cirrhosis and liver failure. The prevalence of AMA in PBC is more than 90% and they can precede long before the clinical symptoms. AMA are conventionally detected by indirect immunofluorescence (IIF) using rodent liver, kidney, and stomach sections as substrates. Additionally, different PBC-specific anti-nuclear autoantibodies (ANA) can be observed in 30% of patients presenting with multiple nuclear dot or nuclear membrane staining patterns, which preferentially are identified using HEp-2 cells as substrate. The identification of the major PBC-specific mitochondrial and nuclear targets has allowed the generation of monospecific antigenic targets which are increasingly used in solid-phase assays for routine detection of AMA and ANA in mono- or multiparametric screen test systems. In the present paper, we give an overview of the diagnostic significance of autoantibodies in PBC, discuss the competencies of different techniques used for their determination and propose an effective diagnostic strategy., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Cardiac autoimmunity has been widely studied over the last years. A lot of cardiac antigens have been identified. Laboratory tests for detection of antibodies against the heart are very helpful in diagnosing and monitoring cardiac autoimmune diseases, but the prevalence of anti-heart antibodies varies a lot between the tests. The aim of this paper is to review the number of laboratory assays used today and to determine the most suitable test for detection of cardiac autoantibodies in human serum.

Background: Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose of oral glucose lowering drugs and their possible side effects., Aim: To assess which clinical features predict the presence or absence of LADA in patients older than 25 years presenting with hyperglycemia., Methods: A structured Medline and Embase search was conducted. Titles and abstracts were screened using predetermined selection criteria. Critical appraisal was based on standardized validity criteria for diagnostic research., Results: One-hundred and eighty-four papers were retrieved of which after assessment of relevance and validity 2 studies remained for further analysis. One study reported a probability of LADA of 0.99 with one or two out of the following five clinical features: age at onset <50 years; acute symptoms; BMI<25 kg/m(2); a history of autoimmune disease; a family history positive for diabetes mellitus. The other study reported a probability of LADA of zero with none of the following clinical features and of 0.32 with one out of three: fasting blood glucose> or =15 mmol/l and/or HbA(1c)> or =10%; 10% reduction in body weight in the previous 3 months; BMI<25 kg/m(2)., Conclusion: Further testing for LADA by measurement of autoimmune antibodies appears to be unnecessary in the absence of a specific set of clinical features. Before initiating therapy applying the above criteria may help to separate LADA from usual type 2 diabetes.

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with intestinal gluten sensitivity. Epidermal transglutaminase (TGe) and closely related tissue transglutaminase (tTG) are considered to be autoantigens in DH, because a majority of DH patients have IgA specific for TGe and for tTG. It is unknown where and how these autoantigen-specific IgAs are generated in DH. Results reported in this paper on nine DH patients on a gluten containing diet demonstrate that the levels of circulating anti-tTG IgA and anti-TGe IgA in DH are correlated with each other and that both appear to be correlated with the degree (extent) of enteropathy. An analysis of 15 untreated celiac sprue (CS) patients demonstrated that approximately 33% of CS patients had elevated levels of anti-TGe IgA. These results would indicate that intestinal damage is associated with the production of anti-tTG IgA and anti-TGe IgA in DH patients.

Musculoskeletal (MSK) disorders constitute one of the most common clinical presentations to clinical care givers. Within this category of illnesses, systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SjS) and rheumatoid arthritis (RA) are included in the differential diagnosis. A hallmark of SARD is the production of autoantibodies, which are routinely requested as a guide to diagnosis and clinical decision making. The field of serological tests, including the detection of autoantibodies, is complex and often leads to confusion and misunderstanding. When used appropriately, autoantibodies can be a valuable adjunct to the diagnosis, and occasionally therapy and prognosis, of SARD. The role of autoantibody testing and a 'practical' approach to using these tests is the focus of this paper.

Autoimmune (Hashimoto's) thyroiditis is a chronic inflammatory disease which affects >3% of the population and shows an increasing prevalence with increasing age. Anti-thyroid autoantibodies, particularly against thyroperoxidase (also known as thyroid peroxidase or TPO), occur commonly in humans with autoimmune thyroid disease, and assays for anti-TPO autoantibodies are used in clinical diagnosis. In contrast anti-TPO autoantibodies have not been observed in classical mouse models of autoimmune thyroiditis, except in cases where mice were deliberately immunized with TPO. In the past, detection of anti-TPO autoantibodies in mice has relied on an indirect immunofluorescence assay (iIFA) which screens for thyroid follicle membrane staining in frozen sections of mouse thyroid glands. Since recent transgenic mouse models of autoimmune thyroiditis spontaneously develop anti-TPO autoantibodies, an assay other than serial dilution and iIFA would be useful to detect and quantify these autoantibodies. In this paper we describe such an assay, based on the capacity of autoimmune mouse sera to bind to the extracellular domain of mouse TPO which was produced in a radioactively labeled form using a coupled in vitro transcription/translation system. The same approach, using human TPO, could provide a highly sensitive method to detect anti-TPO autoantibodies in humans.

Systemic lupus erythematosus (SLE) is a systemic rheumatic disease characterized clinically by multiorgan involvement and serologically by the occurrence of antinuclear antibodies. SLE patients may present with multiple autoantibodies to cytoplasmic and cell surface antigens as well as to circulating plasma proteins. Another feature of SLE is that serum levels of C-reactive protein (CRP) often remain low despite high disease activity and despite high levels of other acute phase proteins and interleukin-6, i.e. the main CRP inducing cytokine. Apart from its important role as a laboratory marker of inflammation, CRP attracts increasing interest due to its many intriguing biological functions, one of which is a role as an opsonin contributing to the elimination of apoptotic cell debris, e.g. nucleosomes, thereby preventing immunization against autoantigens. Recently, autoantibodies against CRP and other acute phase proteins have been reported in certain rheumatic conditions, including SLE. Although the presence of anti-CRP autoantibodies does not explain the failed CRP response in SLE, antibodies directed against acute phase proteins have several implications of pathogenetic interest. This paper thus highlights the biological and clinical aspects of native and monomeric CRP and anti-CRP, as well as autoantibodies against mannose-binding lectin, serum amyloid A and serum amyloid P component.