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Plain language summary: The thyroid is a gland located in the neck and is important for many processes in the body. Problems with the thyroid gland are common in women of reproductive age. It is essential to have a normal working thyroid gland in order to achieve a successful pregnancy. One of the most common problems with the thyroid is underactivity (known as hypothyroidism). An early, mild form of an underactive thyroid is called subclinical hypothyroidism. Often people with this condition do not have any symptoms. Another common problem is thyroid autoimmunity. Here, the immune system attacks the thyroid gland, sometimes leading to the development of abnormal thyroid function. This can be diagnosed by the presence of proteins in the bloodstream called antibodies. Mild thyroid problems and the presence of high levels of thyroid antibodies have been linked to miscarriage and premature birth. There is debate in medicine about whether there should be routine testing of thyroid function both in the general population and in individuals who are trying for a baby. In addition, the strategies used to manage certain thyroid problems are questioned. Discussions around testing and subsequent management particularly relate to women with a history of subfertility or repeated miscarriages. This Scientific Impact Paper provides information on thyroid testing and the management of mild thyroid problems and thyroid antibodies in women with a history of subfertility or recurrent miscarriages, using the latest evidence and guidelines. It concludes that there may be a role for treating these women with thyroxine tablets (the hormone produced by the thyroid gland) when subclinical hypothyroidism is present, and gives guidance on the cut‐off levels for treatment. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is increasing in incidence and predictable with measurement of serum islet autoantibodies (iAb) years prior to clinical disease onset. Identifying iAb positive individuals reduces diabetic ketoacidosis and identifies individuals for T1D prevention trials. However, large scale screening for iAb remains challenging as assays have varying sensitivities and specificities, insulin autoantibodies remain difficult to measure and venipuncture is generally required to obtain serum. We developed an approach to reliably measure all four major iAb, including insulin autoantibodies, from dried blood spots (DBS) on filter-paper. By spiking iAb positive serum into iAb negative whole blood in a dose titration, we optimized the conditions for autoantibody elution from filter paper as measured by fluid phase radioimmunoassays. After assessing stability of measuring iAb from DBS over time, we then screened iAb from DBS and the corresponding serum in new-onset T1D (n = 52), and controls (n = 72) which included first-degree relatives of T1D patients. iAb measured from eluted DBS in new-onset T1D strongly correlated with serum measurements (R2 = 0.96 for mIAA, GADA = 0.94, IA-2A = 0.85, ZnT8A = 0.82, p<0.01 for each autoantibody). There were no false positives in control subjects, and 5/6 with previously unknown iAb positivity in sera were detected using DBS. With further validation, measuring iAb from DBS can be a reliable method to screen for T1D risk. [ABSTRACT FROM AUTHOR]

[Display omitted] • A kirigami-and-paste protocol for the fabrication of a paper-based analytical device was developed. • Tumor p53 antigen was covalently immobilized in the paper test zone for p53 autoantibody detection. • Fe 3 O 4 @SiO 2 -prNH 2 -Au@Pd 0.30 NPs-anti-IgG peroxidase-like nanozymes as colorimetric signal generation probe. • Smartphone integrated with a camera and color picker software for rapid quantitative analysis. • Ultrasensitive detection of anti-p53 autoantibody is achieved with pg.mL −1 sensitivity. Ultrasensitive, rapid, and low-cost paper-based immunodevice integrating a smartphone platform to detect ultra-low concentrations of tumour-specific anti-p53 autoantibodies (anti-p53aAbs) in human serum samples was developed. The immunodevice was fabricated based on the principles of kirigami (paper cutting and pasting art). It consisted of hydrophilic paper discs sandwiched between a superhydrophobic paper basement and polyethylene terephthalate-ethylene vinyl acetate (PET-EVA) laminate to delineate the sensing discs. The human p53 antigen (p53Ag) was covalently immobilized onto the pre-functionalized paper disc and used as the biorecognition element to capture anti-p53aAbs in human serum samples. The Fe 3 O 4 @SiO 2 -prNH 2 -Au@Pd 0.30 NPs-anti-IgG immunonanoprobes were used as the catalytic label for substrate (TMB/H 2 O 2) oxidation, which generates blue colourimetric spots on the paper sensor. A smartphone installed on a custom-made imaging photo box equipped with colour analysis software was used as a reader to capture and quantitatively analyze the images. The immunodevice exhibited a linear increase in the colour pixel intensity with increasing concentrations of anti-p53aAbs from 10 pg.mL −1 to 25.0 ng.mL −1, with a sensitivity of 1.05 pixel.mL.pg −1 and a detection limit of 3.1 pg.mL −1. The fabricated proof-of-concept immunodevice could provide a simple, affordable, and minimally invasive method for cancer diagnosis at point-of-care. [ABSTRACT FROM AUTHOR]

Reliable autoantibody detection is important for early diagnosis and appropriate treatment of autoimmune disorders. However, in contrast to testing for classical clinical chemistry analytes, autoantibody testing is complex and evolving. Moreover, there is a lack of standardization. Nevertheless, it is important that laboratories that provide autoimmune tests comply with the requirements set forward by general international accreditation bodies. In the present manuscript, an ad hoc committee of the European Autoimmunity Standardisation Initiative (EASI) group provides background information on accreditation and identifies the minimum requirements needed to set up an accredited autoimmunity lab and to ensure that high-quality results are provided (in terms of personnel, procedures, validation, quality control, and reporting). Areas in which additional work needs to be done are identified. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP), a common autoimmune blistering disease, is increasing in incidence and conveys a high mortality. Detection of autoantibodies targeting the noncollagenous 16A (NCI6A) domain of type XVII collagen using enzyme-linked immunosorbent assay (ELISA) has demonstrated high sensitivity and specificity for diagnosing BP. We have developed a rapid, low-cost, and widely applicable ELISA-based system to detect the NC16A autoimmune antibody and then diagnose and monitor BP disease activity using a piece of filter paper, a wax-printer, and NC16A antigens. Both sera and/or blister fluids from 14 untreated BP patients were analyzed. The control group included healthy volunteers and patients with other blistering disorders such as pemphigus vulgaris. In our established paper-based ELISA (P-ELISA) system, only 2 μL of serum or blister fluid and 70 min were required to detect anti-NC16A autoimmune antibodies. The relative color intensity was significantiy higher in the BP group than in the control groups when using either serum (P < 0.05) or blister fluid (P < 0.001) specimens from BP patients. The results of P- ELISA were moderately correlated with the titer of the commercial ELISA kit (MBL, Japan) (rho = 0.5680, P = 0.0011). This newly developed system allows for rapid and convenient diagnosis and/or monitoring of BP disease activity. [ABSTRACT FROM AUTHOR]

Thrombopoietin, the primary regulator of blood platelet production, was postulated to exist in 1958, but was only proven to exist when the cDNA for the hormone was cloned in 1994. Since its initial cloning and characterization, the hormone has revealed many surprises. For example, instead of acting as the postulated differentiation factor for platelet precursors, megakaryocytes, it is the most potent stimulator of megakaryocyte progenitor expansion known. Moreover, it also stimulates the survival, and in combination with stem cell factor leads to the expansion of hematopoietic stem cells. All of these growth-promoting activities have resulted in its clinical use in patients with thrombocytopenia and aplastic anemia, although the clinical development of the native molecule illustrated that "it's not wise to mess with mother nature", as a highly engineered version of the native hormone led to autoantibody formation and severe thrombocytopenia. Finally, another unexpected finding was the role of the thrombopoietin receptor in stem cell biology, including the development of myeloproliferative neoplasms, an important disorder of hematopoietic stem cells. Overall, the past 30 years of clinical and basic research has yielded many important insights, which are reviewed in this paper. [ABSTRACT FROM AUTHOR]

There is limited information regarding the use of dried capillary blood spots collected on a filter paper (FP) to test for islet cell antibodies. The aim of this study was to validate the use of dried capillary blood spots collected on a FP for the analysis of islet cell antibodies. FP eluates were tested using both single and combined assay for antibodies to glutamic acid decarboxylase (GADA) and/or to the protein tyrosine phosphatase like IA-2 (IA-2A), and a single assay for antibodies to insulin (IAA). The results were compared with those of serum assays. Ninety-one subjects were studied. Forty had Type 1 diabetes mellitus (T1DM) and 51 were first-degree relatives (FDR) of patients with T1DM. The GADA and IA-2A were measured by radio-binding assays, which utilize 35S-labeled GAD65 and IA-2. IAA was measured by a microtiter plate assay using 125I-labeled insulin. Twenty-six of those with T1DM (65%) and 5 of the FDRs (10%) had at least 1 positive test on the single serum assays. The FP combi-assay for GADA and IA-2A had 97.8% concordance rate when compared with serum single assays for GADA and IA-2A. The concordance rate for individual assays were 96.7% for GADA, and 100% for both IA-2A and IAA There was significant correlation of the antibody levels between FP and serum specimen for all 3 antibodies. We conclude that antibody screening performed using dried capillary blood spots collected on a FP correlates well with serum assays, and provides an easy alternative for population screening. [ABSTRACT FROM AUTHOR]

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria ( CU) patient sera have been demonstrated against Ig E and Fcε RIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to Ig G1 and Ig G3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA- DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new 'gold standard' for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity. [ABSTRACT FROM AUTHOR]

The amyloid hypothesis has so far been at the forefront of explaining the pathogenesis of Alzheimer's Disease (AD), a progressive neurodegenerative disorder that leads to cognitive decline and eventual death. Recent evidence, however, points to additional factors that contribute to the pathogenesis of this disease. These include the neurovascular hypothesis, the mitochondrial cascade hypothesis, the inflammatory hypothesis, the prion hypothesis, the mutational accumulation hypothesis, and the autoimmunity hypothesis. The purpose of this review was to briefly discuss the factors that are associated with autoimmunity in humans, including sex, the gut and lung microbiomes, age, genetics, and environmental factors. Subsequently, it was to examine the rise of autoimmune phenomena in AD, which can be instigated by a blood-brain barrier breakdown, pathogen infections, and dysfunction of the glymphatic system. Lastly, it was to discuss the various ways by which immune system dysregulation leads to AD, immunomodulating therapies, and future directions in the field of autoimmunity and neurodegeneration. A comprehensive account of the recent research done in the field was extracted from PubMed on 31 January 2022, with the keywords "Alzheimer's disease" and "autoantibodies" for the first search input, and "Alzheimer's disease" with "IgG" for the second. From the first search, 19 papers were selected, because they contained recent research on the autoantibodies found in the biofluids of patients with AD. From the second search, four papers were selected. The analysis of the literature has led to support the autoimmune hypothesis in AD. Autoantibodies were found in biofluids (serum/plasma, cerebrospinal fluid) of patients with AD with multiple methods, including ELISA, Mass Spectrometry, and microarray analysis. Through continuous research, the understanding of the synergistic effects of the various components that lead to AD will pave the way for better therapeutic methods and a deeper understanding of the disease. [ABSTRACT FROM AUTHOR]

To understand how COVID-19 may induce autoimmune diseases, we have been compiling an atlas of COVID autoantigens (autoAgs). Using dermatan sulfate (DS) affinity enrichment of autoantigenic proteins extracted from HS-Sultan lymphoblasts, we identified 362 DS-affinity proteins, of which at least 201 (56%) are confirmed autoAgs. Comparison with available multi-omic COVID data shows that 315 (87%) of the 362 proteins are affected in SARS-CoV-2 infection via altered expression, interaction with viral components, or modification by phosphorylation or ubiquitination, at least 186 (59%) of which are known autoAgs. These proteins are associated with gene expression, mRNA processing, mRNA splicing, translation, protein folding, vesicles, and chromosome organization. Numerous nuclear autoAgs were identified, including both classical antinuclear antibodies (ANAs) and extractable nuclear antigens (ENAs) of systemic autoimmune diseases and unique autoAgs involved in the DNA replication fork, mitotic cell cycle, or telomerase maintenance. We also identified many uncommon autoAgs involved in nucleic acid and peptide biosynthesis and nucleocytoplasmic transport, such as aminoacyl-tRNA synthetases. In addition, this study found autoAgs that potentially interact with multiple SARS-CoV-2 Nsp and Orf components, including CCT/TriC chaperonin, insulin degrading enzyme, platelet-activating factor acetylhydrolase, and the ezrin-moesin-radixin family. Furthermore, B-cell-specific IgM-associated endoplasmic reticulum (ER) complex (including MBZ1, BiP, heat shock proteins, and protein disulfide-isomerases) is enriched by DS-affinity and up-regulated in B-cells of COVID-19 patients, and a similar IgH-associated ER complex was also identified in autoreactive pre-B1 cells in our previous study, which suggests a role of autoreactive B1 cells in COVID-19 that merits further investigation. In summary, this study demonstrates that virally infected cells are characterized by alterations of proteins with propensity to become autoAgs, thereby providing a possible explanation for infection-induced autoimmunity. The COVID autoantigen-ome provides a valuable molecular resource and map for investigation of COVID-related autoimmune sequelae and considerations for vaccine design. This paper investigates the autoantigenic proteome ('autoantigen-ome') of human B cells and shows that a large fraction of these DS-binding autoantigens is affected during SARS-CoV-2 infection, giving rise to a diverse pool of autoAgs that may lead to infection-induced autoimmune diseases. The COVID autoantigen-ome provided in this paper may serve as a molecular map and resource for investigating autoimmune phenomena of SARS-CoV-2 infection and its long-term sequelae. Understanding immunogenic proteins of COVID may also enhance vaccine target design. [ABSTRACT FROM AUTHOR]

In order to understand autoimmune phenomena contributing to the pathophysiology of COVID-19 and post-COVID syndrome, we have been profiling autoantigens (autoAgs) from various cell types. Although cells share numerous autoAgs, each cell type gives rise to unique COVID-altered autoAg candidates, which may explain the wide range of symptoms experienced by patients with autoimmune sequelae of SARS-CoV-2 infection. Based on the unifying property of affinity between autoAgs and the glycosaminoglycan dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of human Jurkat T-cells, of which at least 105 (75%) are known targets of autoantibodies. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) DS-affinity proteins are altered at protein and/or RNA levels in SARS-CoV-2-infected cells or patients, with at least 94 being known autoAgs in a wide spectrum of autoimmune diseases and cancer. Protein alterations by ubiquitination and phosphorylation during the viral infection are major contributors of autoAgs. The autoAg protein network is significantly associated with cellular response to stress, apoptosis, RNA metabolism, mRNA processing and translation, protein folding and processing, chromosome organization, cell cycle, and muscle contraction. The autoAgs include clusters of histones, CCT/TriC chaperonin, DNA replication licensing factors, proteasome and ribosome proteins, heat shock proteins, serine/arginine-rich splicing factors, 14-3-3 proteins, and cytoskeletal proteins. AutoAgs, such as LCP1 and NACA, that are altered in the T cells of COVID patients may provide insight into T-cell responses to viral infection and merit further study. The autoantigen-ome from this study contributes to a comprehensive molecular map for investigating acute, subacute, and chronic autoimmune disorders caused by SARS-CoV-2. Based on the unique affinity between autoantigens (autoAgs) and dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of Jurkat T-cells, with at least 105 (75%) being known targets of autoantibodies in various autoimmune diseases and cancer. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) DS-affinity proteins are altered in SARS-CoV-2-infected cells or patients. AutoAgs, such as LCP1 and NACA, that are altered in the T cells of COVID-19 patients may provide insight into T-cell responses during viral infection. [ABSTRACT FROM AUTHOR]

Deficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed ‘autoimmune thrombotic thrombocytopenic purpura’. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein A and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2–3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the prevalence of basement membrane zone (BMZ) antibodies, their subtypes and clinical correlations in 96 patients attending the Oxford vulval clinic with lichen sclerosus (LS) of the vulva. Indirect immunofluorescence of serum (intact and split skin) to immunoglobulin (Ig)G was performed looking for the presence or absence of staining at the BMZ. Eighteen patients' sera (14 with positive indirect immunofluorescence to IgG) were examined for IgG antibodies of subclasses IgG1, 2 and 3, and 23 sera were examined for IgG4 subclass. Immunoblotting was performed in seven patients, and showed antibodies to BP180 in six patients and BP230 in one. One-third of patients with vulval LS had BMZ antibodies binding to the epidermal side of salt split skin. Immunoblotting showed antibodies to BP180 collagen XVII (six of seven patients) and BP230 in one. The subclasses were chiefly IgG1 and 2, different from those seen in bullous pemphigoid. No clinical correlation was found between the presence of antibodies and the presence of erosions, severity of scarring, age of onset of disease or response to treatment. These antibodies may be a reflection of a tendency to produce autoantibodies or be relevant to pathogenesis. [ABSTRACT FROM AUTHOR]

In cold agglutinin disease, monoclonal red blood cell autoantibodies, termed cold agglutinins, induce haemolysis in patients exposed to the cold. Commonly, these autoantibodies are directed against the developmentally regulated I/i blood groups. A second blood group system, the Pr system (located on glycophorins), is involved less frequently. Anti-Pr cold agglutinins recognize either alpha 2,3- or alpha 2,6-linked N-acetylneuraminic acid as the immunodominant group. Cold agglutinins of anti-I/i specificity show a remarkable restriction in their genomic repertoire of the immunoglobulin heavy and light-chain immunoglobulin-variable domain (i.e. exclusive use of VH4-34 in heavy chains). For anti-Pr cold agglutinins, preliminary data on the repertoire of the light-chain variable domain indicate a preference for the subgroup Vkappa IV. To elucidate restrictions in the light-chain variable-domain subgroup repertoire of anti-Pr cold agglutinins systematically, and to discuss these results in the context of their anti-Pr1–3 subclassification and immunodominant sialic acid, light chains in 13 anti-Pr cold agglutinins were investigated. The anti-Pr light chains were isolated using temperature-dependent absorption/elution techniques. Subsequently, they were subjected to N-terminal Edman degradation, and the light chain Vkappa subgroup was affiliated using the Kabat database. Five of 13 (38%) light chains belonged to Vkappa IV, five of 13 (38%) to Vkappa I and three of 13 (23%) to Vkappa III. Anti-Pr with Vkappa IV subgroup light chains exclusively recognized alpha 2,3-linked N-acetylneuraminic acid. Including data from the literature, the repertoire of the light-chain variable domain in pathological anti-Pr cold agglutinins exhibits a clear bias towards the use of the single germline gene-derived subgroup, Vkappa IV (eight of 17 or 47%). The association of Vkappa IV subgroup light chain-containing anti-Pr cold agglutinins with binding to alpha 2,3-, but not alpha 2,6-linked N-acetyneuraminic acid raises speculations about a possible role of subgroup-derived determinants in anti-Pr binding. [ABSTRACT FROM AUTHOR]

Administration of diclofenac may lead to immune haemolytic anaemia (IHA) owing to the presence of drug-dependent antibodies and/or autoantibodies. A relationship with oral or intramuscular drug administration is unknown. Here, we describe a patient who apparently tolerated oral diclofenac but developed severe IHA following intramuscular injection of the drug. A 66-year-old-female was admitted to hospital because of jaundice and nausea, which were initially presumed to be manifestations of a postcholecystectomy syndrome. The patient soon developed haemolysis and renal failure. Although the symptoms and signs were suggestive of autoimmune haemolytic anaemia (AIHA), the patient had diclofenac-induced IHA. Serological testing, including detection of drug-dependent antibodies, was performed using standard techniques. The patient's serum was found to contain a highly reactive diclofenac-dependent red cell antibody of the immune complex type (titre 256 000). She recovered after 7 weeks of treatment with prednisolone, blood transfusions, haemodialysis and plasma exchange. Diclofenac-induced IHA should always be considered when a patient on diclofenac develops haemolysis. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised by pathological processes involving autoimmunity, vasculopathy and resultant extensive skin and organ fibrosis. Recent studies have demonstrated activation and aberrant wound healing responses in the epithelial layer of the skin in this disease, implicating the epithelial keratinocytes as a source of pro-fibrotic and inflammatory mediators. In this paper, we investigated the role of Immunoglobulin G (IgG) autoantibodies directed against epithelial cells, as potential initiators and propagators of pathological keratocyte activation and the ensuing SSc fibrotic cascade. A keratinocyte cell-based ELISA is used to evaluate the binding of SSc IgG. SSc skin biopsies were stained by immunofluorescence for the presence of IgG in the keratinocyte layer. Moreover, IgG purified from SSc sera was evaluated for the potential to activate keratinocytes in tissue culture and to induce TLR2 and 3 signalling in reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes and the activation of these cells leading to the release of IL-1α, representing a potential initiating pathway in this disease. [ABSTRACT FROM AUTHOR]

An increased risk of atherosclerotic and thrombotic complications characterizes connective tissue diseases. Endothelial dysfunction is the basis for the initiation and progression of atherosclerosis and thrombosis. We present systemic lupus erythematosus (SLE) as a model rheumatic disease with endothelial dysfunction and discuss its mechanisms, factors that influence the early onset and rapid progression of atherosclerosis, and the increased risk of thromboembolic events. We focus on established methods to improve endothelium function, including statins, antiplatelet, and antithrombotic therapy. Hypercoagulable and hypofibrinolitic states and a hyperinflammatory response characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several pathogenic mechanisms are typical for an acute phase of Covid-19 post-Covid syndrome and connective tissue diseases: endothelial dysfunction, elevated antiphospholipid antibody titer, activation of the complement system, and formation of extracellular neutrophil traps (NET). The current review discusses the mechanisms underlying SLE and the COVID-19 in the context of endothelial function, atherosclerosis, and thrombosis (Graphical abstract). Key Points • The pathophysiology of systemic lupus erythematosus (SLE) and Covid-19 shows some similarities, such as endothelial cell activation and dysfunction, the activation of complementary systems, the presence of antiphospholipid antibodies, and the formation of extracellular neutrophil traps. • Autoimmunity in both diseases creates the basis for hyperinflammatory, hypercoagulable, and hypofibrinolitic states and their thromboembolic complications. • This paper presents our perspective on the mechanisms behind the cardiovascular manifestations of SLE and COVID-19, with a particular emphasis on endothelial dysfunction. Covid-19 and systemic lupus erythematosus—potential similarities in pathophysiology. Figures of the panel illustrate the clinical manifestations of endothelial dysfunction, atherosclerosis, and thromboembolism, including coronary artery disease ([A] coronary angiography with left anterior descending artery stenosis and [B] scintigraphy with reduced perfusion in the myocardial apical segments), stroke ([C] carotid angiography, left carotid artery occlusion) and pulmonary embolism ([D]computed tomography with thrombus in the right pulmonary artery). [ABSTRACT FROM AUTHOR]

Objective: Sudden sensorineural hearing loss is considered idiopathic in up to 90 per cent of cases. This study explored the role of blood tests as biomarkers for the diagnosis and prognosis of sudden sensorineural hearing loss. Method: Two researchers filtered 34 papers into the final review. This review was pre-registered on the Prospero database and conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Results: Raised inflammatory markers are almost universal in sudden sensorineural hearing loss, suggesting an inflammatory or autoimmune process. The most useful biomarkers are neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and fibrinogen level. Focused investigations should be deployed on a case-by-case basis to identify underlying metabolic, infective and autoimmune conditions. Conclusion: A full blood count and coagulation screen (fibrinogen) is recommended in all cases of sudden sensorineural hearing loss. These are inexpensive, accessible and offer as much diagnostic and prognostic information as any other biomarker. There is emerging evidence regarding specific biomarkers for sudden sensorineural hearing loss prognosis, with heat shock protein-70, anti-endothelial cell antibody and prestin demonstrating potential; investigation of their validity through prospective, controlled research is recommended. [ABSTRACT FROM AUTHOR]

Anticytokine autoantibodies (ACAAs) can cause adult onset immunodeficiencies which mimic primary immunodeficiencies and can present as refractory and severe fungal infections. This paper provides an overview of the role of innate immunity, including key cytokines, in fungal infections and then describes four clinical scenarios where ACAAs are associated with severe presentations of a fungal infection: (1) Talaromyces marneffei infection and anti-interferon-γ, (2) histoplasmosis and anti-interferon-γ, (3) Cryptococcus gattii infection and anti-GM-CSF, and (4) mucocutaneous candidiasis and anti-IL-17A/F (IL-22). Testing for ACAAs and potential therapeutic options are discussed. [ABSTRACT FROM AUTHOR]

As the number of reports of post-acute COVID-19 musculoskeletal manifestations is rapidly rising, it is important to summarize the current available literature in order to shed light on this new and not fully understood phenomenon. Therefore, we conducted a systematic review to provide an updated picture of post-acute COVID-19 musculoskeletal manifestations of potential rheumatological interest, with a particular focus on joint pain, new onset of rheumatic musculoskeletal diseases and presence of autoantibodies related to inflammatory arthritis such as rheumatoid factor and anti-citrullinated protein antibodies. We included 54 original papers in our systematic review. The prevalence of arthralgia was found to range from 2% to 65% within a time frame varying from 4 weeks to 12 months after acute SARS-CoV-2 infection. Inflammatory arthritis was also reported with various clinical phenotypes such as symmetrical polyarthritis with RA-like pattern similar to other prototypical viral arthritis, polymyalgia-like symptoms, or acute monoarthritis and oligoarthritis of large joints resembling reactive arthritis. Moreover, high figures of post-COVID-19 patients fulfilling the classification criteria for fibromyalgia were found, ranging from 31% to 40%. Finally, the available literature about prevalence of rheumatoid factor and anti-citrullinated protein antibodies was largely inconsistent. In conclusion, manifestations of rheumatological interest such as joint pain, new-onset inflammatory arthritis and fibromyalgia are frequently reported after COVID-19, highlighting the potential role of SARS-CoV-2 as a trigger for the development of autoimmune conditions and rheumatic musculoskeletal diseases. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyps (CRSwNP) has long been considered a benign, chronic inflammatory, and hyperplastic disease. Recent studies have shown that autoimmune-related mechanisms are involved in the pathology of nasal polyps. Activated plasma cells, eosinophils, basophils, innate type 2 lymphocytes, mast cells, and proinflammatory cytokine in polyp tissue indicate the mobilization of innate and adaptive immune pathways during polyp formation. The discovery of a series of autoantibodies further supports the autoimmune nature of nasal polyps. Local homeostasis dysregulation, infection, and chronic inflammation may trigger autoimmunity through several mechanisms, including autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, activation or inhibition of receptors, bystander activation, dysregulation of Toll-Like Receptors (TLRs), epitope spreading, autoantigens complementarity. In this paper, we elaborated on the microbiome-mediated mechanism, abnormal host immunity, and genetic changes to update the role of autoimmunity in the pathogenesis of chronic rhinosinusitis with nasal polyps. [ABSTRACT FROM AUTHOR]

This paper presents a model‐based method for clustering multivariate binary observations that incorporates constraints consistent with the scientific context. The approach is motivated by the precision medicine problem of identifying autoimmune disease patient subsets or classes who may require different treatments. We start with a family of restricted latent class models or RLCMs. However, in the motivating example and many others like it, the unknown number of classes and the definition of classes using binary states are among the targets of inference. We use a Bayesian approach to RLCMs in order to use informative prior assumptions on the number and definitions of latent classes to be consistent with scientific knowledge so that the posterior distribution tends to concentrate on smaller numbers of clusters and sparser binary patterns. The paper derives a posterior sampling algorithm based on Markov chain Monte Carlo with split‐merge updates to efficiently explore the space of clustering allocations. Through simulations under the assumed model and realistic deviations from it, we demonstrate greater interpretability of results and superior finite‐sample clustering performance for our method compared to common alternatives. The methods are illustrated with an analysis of protein data to detect clusters representing autoantibody classes among scleroderma patients. [ABSTRACT FROM AUTHOR]

The article presents abstracts on research related to women's health which include the association between maternal folate-receptor autoantibodies and neural-tube defects, a prospective cohort study which examines the risk of pre-eclampsia in first and subsequent pregnancies, and the effectiveness of progesteron in reducing preterm birth in twin pregnancy.

Pernicious anemia is a megaloblastic type of anemia caused by vitamin B12 deficiency, mediated by intrinsic factor deficiency, associated with atrophic body gastritis, confirmed by the presence of gastric body atrophy and parietal cells pathology in the stomach. It shares with helicobacter pylori gastritis the autoimmune character and in both exist some autoantibodies. Methods: A search for papers on epidemiology and pathophysiology of pernicious anemia was conducted using the keywords: Helicobacter pylori, gastritis, anemia, vitamin B12, pathophysiology, epidemiology. Then snowballing technique was used to find more references. Results: Shared features of both types of gastritis and evidence from the published papers confirmed that helicobacter pylori play a role in the pathophysiology of pernicious anemia. Conclusion: There is some evidence in the literature that some individuals with specific susceptibility could develop pernicious anemia when infected by helicobacter pylori gastritis. [ABSTRACT FROM AUTHOR]

Rapidly progressive cerebellar ataxia is a classical paraneoplastic neurological syndrome associated with different autoantibodies and typical demographic characteristics, extracerebellar signs, tumor association, and prognosis. Anti-Tr/anti-Delta/Notch-like epidermal growth factor-related receptor (DNER) antibody is one of the associated antibodies. Given the rarity of this condition, our current knowledge is based on case reports and small case series. In order to improve our understanding of these conditions, we conducted a systematic review of the literature. Our study followed the PRISMA reporting guidelines. Studies of patients with the presence of anti-Tr/DNER antibodies in serum or cerebrospinal fluid (CSF) were included. We extract data information related to study characteristics, demographics, clinical symptoms, tumor association, neuroimaging, and cerebrospinal fluid analysis. Out of 131 records, we analyzed 17 papers, including a total of 85 patients with anti-Tr/DNER antibody–associated cerebellar ataxia. We confirmed that this disease occurred mostly in middle-aged males. Isolated cerebellar ataxia was the most common presentation. Extracerebellar features were rare (8%). Ninety-one percent of the patients presented an associated tumor, being Hodgkin lymphoma the most common. Abnormal neuroimaging patterns included cerebellar atrophy (19%) and cerebellar hypersignal (6%). Cerebrospinal fluid was inflammatory in 64% of the patients. Oncological response was complete in 88%, but neurological prognosis was poor with only 41% of the patients presenting significant neurological improvement at the last follow up. Anti-Tr/DNER antibodies should be tested in rapid progressive cerebellar ataxia. Oncological response is excellent; however, many patients do not improve from their cerebellar ataxia. [ABSTRACT FROM AUTHOR]

Objectives: Type 1 diabetes mellitus (T1DM) is a well-known autoimmune disease, characterized by β-cell destruction in pancreas islet cells, which results insulin deficiency and subsequent hyperglycemic sequelae. While there is screening for type 2 DM that leads to better glycemic control and outcome, the majority of T1DM patients are diagnosed when much of the pancreatic cells and their function are disturbed. The aim of this article is to present an overview of the effective factors in the positivity of Glutamic acid decarboxylase antibody)GADA(and identifying the high-risk individuals for T1DM. Methods: We searched English literature available at National Library of Medicine via PubMed, and Google Scholar through December 2020. Finally, 79 papers have been included in the study. Studies were summarized based on the number of positive autoantibodies and onset of T1DM over time and GADA correlation with different variables. Conclusions: GADA is an easy marker to measure that can be detected many months prior to the clinical presentation and remains positive even after early childhood. [ABSTRACT FROM AUTHOR]

Since the onset of the COVID-19 pandemic, numerous publications have appeared describing autoimmune pathologies developing after a coronavirus infection, with several papers reporting autoantibody production during the acute period of the disease. Several viral diseases are known to trigger autoimmune processes, and the appearance of catalytic antibodies with DNase activity is one of the earliest markers of several autoimmune pathologies. Therefore, we analyzed whether IgG antibodies from blood plasma of SARS-CoV-2 patients after recovery could bind and hydrolyze DNA. We analyzed how vaccination of patients with adenovirus Sputnik V vaccine influences the production of abzymes with DNase activity. Four groups were selected for the analysis, each containing 25 patients according to their relative titers of antibodies to S-protein: with high and median titers, vaccinated with Sputnik V with high titers, and a control group of donors with negative titers. The relative titers of antibodies against DNA and the relative DNase activity of IgGs depended very much on the individual patient and the donor, and no significant correlation was found between the relative values of antibodies titers and their DNase activity. Our results indicate that COVID-19 disease and vaccination with adenoviral Sputnik V vaccine do not result in the development or enhancement of strong autoimmune reactions as in the typical autoimmune diseases associated with the production of anti-DNA and DNA hydrolyzing antibodies. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the deadliest gynecological cancer, leading to over 152,000 deaths each year. A late diagnosis is the primary factor causing a poor prognosis of ovarian cancer and often occurs due to a lack of specific symptoms and effective biomarkers for an early detection. Currently, cancer antigen 125 (CA125) is the most widely used biomarker for ovarian cancer detection, but this approach is limited by a low specificity. In recent years, multimarker panels have been developed by combining molecular biomarkers such as human epididymis secretory protein 4 (HE4), ultrasound results, or menopausal status to improve the diagnostic efficacy. The risk of ovarian malignancy algorithm (ROMA), the risk of malignancy index (RMI), and OVA1 assays have also been clinically used with improved sensitivity and specificity. Ongoing investigations into novel biomarkers such as autoantibodies, ctDNAs, miRNAs, and DNA methylation signatures continue to aim to provide earlier detection methods for ovarian cancer. This paper reviews recent advancements in molecular biomarkers for the early detection of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) is the most frequent chronic autoimmune disease in childhood and adolescence, its incidence is increasing particularly in toddlers and preschool children, and up to 60% of young patients present with diabetic ketoacidosis (DKA), a severe and life-threatening complication. So far, the majority of screening efforts have been performed in the at-risk group, i.e., relatives of people with T1D; anyhow, around 90% of young patients who eventually develop T1D do not have a family history. Summary: Some studies in Europe and the USA have clearly shown that a public health screening of children (with positive autoantibodies) is effective in reducing the prevalence of DKA by more than 10 times, decreasing the rate of hospitalization and its costs, providing psychological, emotional, and social support to children and their families. In addition, several treatments and trials are available for children with stage 2 and stage 3 T1D. There is still room for improvement of sensitivity, specificity, positive and negative predictive value in a population screening program; anyhow, there is vivid debate on the opportunity for a screening program in the general population of children at risk for developing T1D. Key Messages: This paper, endorsed by the European Society for Paediatric Endocrinology (ESPE), discusses the issues of a screening program in the general population with the hope that uncertainties and difficulties in this field will be overcome by better screening methods, improved cost-effectiveness, reliable treatments for secondary prevention, and relevant delay in clinically evident T1D in children and adolescents. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder is an increasingly prevalent neurodevelopmental disorder in the world today, with an estimated 2% of the population being affected in the USA. A major complicating factor in diagnosing, treating, and understanding autism spectrum disorder is that defining the disorder is solely based on the observation of behavior. Thus, recent research has focused on identifying specific biological abnormalities in autism spectrum disorder that can provide clues to diagnosis and treatment. Biomarkers are an objective way to identify and measure biological abnormalities for diagnostic purposes as well as to measure changes resulting from treatment. This current opinion paper discusses the state of research of various biomarkers currently in development for autism spectrum disorder. The types of biomarkers identified include prenatal history, genetics, neurological including neuroimaging, neurophysiologic, and visual attention, metabolic including abnormalities in mitochondrial, folate, trans-methylation, and trans-sulfuration pathways, immune including autoantibodies and cytokine dysregulation, autonomic nervous system, and nutritional. Many of these biomarkers have promising preliminary evidence for prenatal and post-natal pre-symptomatic risk assessment, confirmation of diagnosis, subtyping, and treatment response. However, most biomarkers have not undergone validation studies and most studies do not investigate biomarkers with clinically relevant comparison groups. Although the field of biomarker research in autism spectrum disorder is promising, it appears that it is currently in the early stages of development. [ABSTRACT FROM AUTHOR]

Autoantibodies against the complement component C1q (anti-C1q) are among the main biomarkers in lupus nephritis (LN) known to contribute to renal injury. C1q, the recognition subcomponent of the complement classical pathway, forms a heterotetrameric complex with C1r and C1s, and can also associate a central complement regulator and C1 Inhibitor (C1-Inh). However, the frequency and the pathogenic relevance of anti-C1r, anti-C1s and anti-C1-Inh autoantibodies remain poorly studied in LN. In this paper, we screened for anti-C1q, anti-C1r, anti-C1s and anti-C1-Inh autoantibodies and evaluated their association with disease activity and severity in 74 LN patients followed up for 5 years with a total of 266 plasma samples collected. The presence of anti-C1q, anti-C1r, anti-C1s and anti-C1-Inh was assessed by ELISA. IgG was purified by Protein G from antigen-positive plasma and their binding to purified C1q, C1r and C1s was examined by surface plasmon resonance (SPR). The abilities of anti-C1q, anti-C1r and anti-C1s binding IgG on C1 complex formation were analyzed by ELISA. The screening of LN patients' plasma revealed 14.9% anti-C1q positivity; only 4.2%, 6.9% and 0% were found to be positive for anti-C1r, anti-C1s and anti-C1-Inh, respectively. Significant correlations were found between anti-C1q and anti-dsDNA, and anti-nuclear antibodies, C3 and C4, respectively. High levels of anti-C1q antibodies were significantly associated with renal histologic lesions and correlated with histological activity index. Patients with the most severe disease (A class according to BILAG Renal score) had higher levels of anti-C1q antibodies. Anti-C1r and anti-C1s antibodies did not correlate with the clinical characteristics of the LN patients, did not interfere with the C1 complex formation, and were not measurable via SPR. In conclusion, the presence of anti-C1q, but not anti-C1s or anti-C1r, autoantibodies contribute to the autoimmune pathology and the severity of LN. [ABSTRACT FROM AUTHOR]

Simple Summary: Myocarditis is the inflammation of the heart muscle, and viral infections are a common cause of this disease. Myocarditis in some patients can progress to dilated cardiomyopathy (DCM). The mouse model of coxsackievirus B3 (CVB3) is commonly used to understand this disease progression in DCM patients. In this paper, we have attempted to analyze antibodies for heart antigens that could be produced as a result of heart damage in animals infected with CVB3 using a technique called Phage ImmunoPrecipitation Sequencing (PhIP-Seq). The analyses led us to identify antibodies for several proteins that were not previously reported that may have relevance to human disease. Enteroviruses such as group B coxsackieviruses (CVB) are commonly suspected as causes of myocarditis that can lead to dilated cardiomyopathy (DCM), and the mouse model of CVB3 myocarditis is routinely used to understand DCM pathogenesis. Mechanistically, autoimmunity is suspected due to the presence of autoantibodies for select antigens. However, their role continues to be enigmatic, which also raises the question of whether the breadth of autoantibodies is sufficiently characterized. Here, we attempted to comprehensively analyze the autoantibody repertoire using Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a versatile and high-throughput platform, in the mouse model of CVB3 myocarditis. First, PhIP-Seq analysis using the VirScan library revealed antibody reactivity only to CVB3 in the infected group but not in controls, thus validating the technique in this model. Second, using the mouse peptide library, we detected autoantibodies to 32 peptides from 25 proteins in infected animals that are ubiquitously expressed and have not been previously reported. Third, by using ELISA as a secondary assay, we confirmed antibody reactivity in sera from CVB3-infected animals to cytochrome c oxidase assembly factor 4 homolog (COA4) and phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), indicating the specificity of antibody detection by PhIP-Seq technology. Fourth, we noted similar antibody reactivity patterns in CVB3 and CVB4 infections, suggesting that the COA4- and PIK3AP1-reactive antibodies could be common to multiple CVB infections. The specificity of the autoantibodies was affirmed with influenza-infected animals that showed no reactivity to any of the antigens tested. Taken together, our data suggest that the autoantibodies identified by PhIP-Seq may have relevance to CVB pathogenesis, with a possibility that similar reactivity could be expected in human DCM patients. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is a rare autoimmune disorder caused by specific autoantibodies at the neuromuscular junction. MG is classified by the antigen specificity of these antibodies. Acetylcholine receptor (AChR) antibodies are the most common type (74-88%), followed by anti-muscle specific kinase (MuSK) and other antibodies. While all these antibodies lead to neuromuscular transmission failure, the immuno-pathogenic mechanisms are distinct. Complement activation is a primary driver of AChR antibody-positive MG (AChR+ MG) pathogenesis. This leads to the formation of the membrane attack complex and destruction of AChR receptors and the postsynaptic membrane resulting in impaired neurotransmission and muscle weakness characteristic of MG. Broad-based immune-suppressants like corticosteroids are effective in controlling MG; however, their long-term use can be associated with significant adverse effects. Advances in translational research have led to the development of more directed therapeutic agents that are likely to alter the future of MG treatment. Eculizumab is a humanized monoclonal antibody that inhibits the cleavage of complement protein C5 and is approved for use in generalized MG. In this review, we discuss the pathophysiology of MG; the therapeutic efficacy and tolerability of eculizumab, as well as the practical guidelines for its use in MG; future studies exploring the role of eculizumab in different stages and subtypes of MG subtypes; the optimal duration of therapy and its discontinuation; the characterization of non-responder patients; and the use of biomarkers for monitoring therapy are highlighted. Based on the pathophysiologic mechanisms, emerging therapies and new therapeutic targets are also reviewed. [ABSTRACT FROM AUTHOR]

Background: Autoimmune and inflammatory disorder (AIID) prevalence appears to be increasing in all but the world's poorest regions and countries. Autoimmune diseases occur when there is a breakdown in processes that regulate inflammation and self‐recognition by immune cells. Very few field‐based studies have been conducted among Indigenous populations and underserved communities with limited access to medical care. This is due, in part, to the fact that autoimmune diseases are difficult to diagnose, even in clinical settings. In remote field settings these difficulties are compounded by the absence of infrastructure necessary for sample storage and analysis, and the lack of hospital/clinic access for more invasive diagnostic procedures. Because of these limitations, little is known about the prevalence of autoimmunity outside wealthy regions and clinical settings. Aims: The present paper discusses why AIID are of critical importance in human biology research and why more work needs to be devoted to validating, testing, and utilizing methods for detecting autoantibodies and other biomarkers related to autoimmunity in field‐friendly, minimally invasively‐collected samples. This paper reviews some of the methods used to diagnose AIIDs in clinical settings, and highlights methods that have been used in studies within human biology and related fields, emphasizing the invasiveness of specific methods and their feasibility in remote field settings. Discussion and Conclusions: Risk for AIID is affected by several reproductive, dietary, environmental, and genetic factors. Human biologists have unique perspectives that they can bring to autoimmunity research, and more population‐based studies on autoimmunity are needed within these and related fields. [ABSTRACT FROM AUTHOR]

Epilepsy is a common chronic neurological disorder in modern society. One of the major unmet challenges is that current antiseizure medications are basically not disease-modifying. Among the multifaceted etiologies of epilepsy, the role of the immune system has attracted considerable attention in recent years. It is known that both innate and adaptive immunity can be activated in response to insults to the central nervous system, leading to seizures. Moreover, the interaction between ion channels, which have a well-established role in epileptogenesis and epilepsy, and the immune system is complex and is being actively investigated. Some examples, including the interaction between ion channels and mTOR pathways, will be discussed in this paper. Furthermore, there has been substantial progress in our understanding of the pathophysiology of epilepsy associated with autoimmune encephalitis, and numerous neural-specific autoantibodies have been found and documented. Early recognition of immune-mediated epilepsy is important, especially in cases of pharmacoresistant epilepsy and in the presence of signs of autoimmune encephalitis, as early intervention with immunotherapy shows promise. [ABSTRACT FROM AUTHOR]

Background: Autoimmune encephalitis (AE) is an important consideration during the diagnostic work-up of secondary mental disorders. Indeed, isolated psychiatric syndromes have been described in case reports of patients with underlying AE. Therefore, the authors performed a systematic literature review of published cases with AE that have predominant psychiatric/neurocognitive manifestations. The aim of this paper is to present the clinical characteristics of these patients. Methods: The authors conducted a systematic Medline search via Ovid, looking for case reports/series of AEs with antineuronal autoantibodies (Abs) against cell surface/intracellular antigens combined with predominant psychiatric/neurocognitive syndromes. The same was done for patients with Hashimoto encephalopathy/SREAT. Only patients with signs of immunological brain involvement or tumors in their diagnostic investigations or improvement under immunomodulatory drugs were included. Results: We identified 145 patients with AE mimicking predominant psychiatric/neurocognitive syndromes. Of these cases, 64% were female, and the mean age among all patients was 43.9 (±22.1) years. Most of the patients had Abs against neuronal cell surface antigens (55%), most frequently against the NMDA-receptor (N = 46). Amnestic/dementia-like (39%) and schizophreniform (34%) syndromes were the most frequently reported. Cerebrospinal fluid changes were found in 78%, electroencephalography abnormalities in 61%, and magnetic resonance imaging pathologies in 51% of the patients. Immunomodulatory treatment was performed in 87% of the cases, and 94% of the patients responded to treatment. Conclusions: Our findings indicate that AEs can mimic predominant psychiatric and neurocognitive disorders, such as schizophreniform psychoses or neurodegenerative dementia, and that affected patients can be treated successfully with immunomodulatory drugs. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown etiology. Due to the frequent findings of autoimmune antibodies — autoantibodies, immunologic causation of the diffuse alveolar hemorrhage in IPH has been proposed, to assess the prevalence/frequency and type of autoantibodies in pediatric patients with IPH. In addition, the patient demographics, diagnostic modalities used to diagnose IPH, treatment, and outcomes were also evaluated. Scoping review: The PubMed, Medline, and Embase databases were searched with appropriate MeSH terms to identify relevant papers consistent with the defined inclusion criteria. Thirteen observational studies comprising a total of 352 pediatric patients were included in this review. The majority of subjects were girls 217 out of 352 (61.6%). The mean and median ages of patients ranged from 3.1–6.5 years to 2.3–7 years, respectively. In the 10 studies that specified the number of patients in their cohorts with either at least one positive autoantibody or no antibody, the overall prevalence of autoantibodies was 76 out of 288 patients (26.4%). The prevalence of specific antibodies was as follows: ANA, 20.3%; ANCA, 17%; anti-dsDNA, 9.1%; RF, 12%; anti-SMA, 23.2%; and celiac antibodies, 25.9%. Cow's milk protein allergy was present in 16.2% of the children. The significance of an association between IPH and the presence of autoantibodies has not been clarified. The autoantibodies could be suggestive of an overall immune dysregulation rather than causation. However, limited evidence based on a single study suggests that the presence of ANA may be associated with a higher risk of recurrence and worse outcomes. Further research, including prospective studies, will be crucial to explore a possible genetic linkage between vasculitides, systemic rheumatologic diseases, and IPH. Key Points • Approximately one in four pediatric patients with IPH demonstrate autoantibodies. • Antibodies suggestive of celiac disease are the most prevalent autoantibody. • The presence of antinuclear autoantibody may be associated with unfavorable outcomes. • All patients with a positive ANCA demonstrated anti-myeloperoxidase (MPO-ANCA) antibody. [ABSTRACT FROM AUTHOR]

Objective: The incidence of type 1 diabetes (T1D) is increasing, most notably in young children and in racial and ethnic minorities. Historically, screening for risk with T1D‐associated antibodies has been limited to those with a family history, while up to 90% of newly diagnosed patients lack such a family history. To address the needs to screen diverse ethnic groups in the general population, we screened children for T1D‐associated antibodies in the Denver, Colorado metro area at community health fairs. Methods: Children attending health fairs from 2015 to 2018 were offered free T1D screening by measuring the four prototypical T1D‐associated antibodies. A finger stick capillary puncture was performed to collect blood spots on filter paper. Dried blood spots (DBSs) were eluted and antibodies were measured using fluid‐phase radio‐binding assays. Results: At 39 health fairs, children were educated on the signs and symptoms of diabetes, and screened for T1D‐associated antibodies (n = 478), which represented 90% of those that attended. Median age was 9.0 years (range of 1‐18) with diverse ethnic backgrounds: 37% Hispanic, 31% Caucasian, 20% African American, and 12% other. Nine children screened positive for antibodies, single n = 8 and multiple n = 1, and confirmation with serum samples showed excellent correlation to the measurements from DBSs for antibodies directed against GAD, IA‐2, and ZnT8 (P < .01 for each). Conclusions: Screening for T1D risk at community health fairs using DBSs on filter paper is feasible and provides an avenue to screen children from ethnically diverse backgrounds. [ABSTRACT FROM AUTHOR]

Moderate-to-severe systemic lupus erythematosus (SLE) is characterized by extensive autoantibody deposition and persistent autoinflammation. As the existing animal models are limited in accurately reproducing the pathological characteristics of human SLE, we introduced a novel animal model simulating multi-organ autoinflammation through intra-organ injections. The model closely mimicked key features of SLE, including IgG deposition, inflammation, and tissue damage. The model could be used to assess the roles of IgG, immune cells, cytokines, and Fc gamma receptor (FcγR) in the pathogenesis of autoinflammation. The results obtained from this model could be confirmed by lupus MRL/ lpr mice. The review suggested that the diagnostic criteria should be reconsidered to incorporate IgG deposition in tissues and highlighted the limitations of current T-cell and B-cell-focused treatments. To summarize, the IgG deposition model can be used to investigate the pathogenesis and treatment of multi-organ tissue damage associated with SLE. • Introduction of a novel animal model: a new animal model mimicing the pathogenesis of lupus autoantibodies IgG-induced organ-tissue damage. • Comprehensive Exploration and Validation of New Model: The roles of lupus autoantibody IgG, immune cells, cytokines and FcγR in organ tissue inflammation were investigated by using this new model. Confirmation of the results from the new model using lupus-prone MRL/lpr mice. • Implications for SLE Research and Treatment: Importance and convenience of the IgG deposition model in investigating the pathogenesis of SLE and its potential for developing targeted therapies. • This paper significantly contributes to the understanding of SLE pathogenesis by introducing a novel animal model that accurately replicates key aspects of the disease, providing a platform for more effective therapeutic exploration and diagnostic considerations. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren's syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren's syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren's syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren's syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren's syndrome, starting from its pathogenesis to current therapeutic options. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • The use of laboratory tests for systemic lupus erythematosus (SLE) diagnosis and monitoring needs to be optimized. • 9 independent experts from first-order Spanish institutions have drawn up recommendations for SLE diagnosis and monitoring. • Interventions to improve SLE diagnosis and monitoring must be adapted to the level of care. [ABSTRACT FROM AUTHOR]

Sicca syndrome, which is typical for Sjögren's syndrome (SS), both primary (pSS) and secondary (sSS), is relatively often comorbid with other autoimmune diseases. The current classification criteria for SS published in 2016 include only anti-SSA (anti-Ro) autoantibody, while the latest literature proposes that anti-Ro60/anti-Ro52 autoantibody profiles should be used instead, as these two types of antibodies correlate with specific clinical symptoms and laboratory test findings. The paper presents the case of a 41-year-old woman suffering from pSS and her three daughters, who were under observation for rheumatic disorders due to sicca symptoms, especially pSS, as well as a discussion on separate determination of anti-Ro60 and anti-Ro52 autoantibodies based on current literature in the PubMed database. When testing with antinuclear antibodies, the Ro60+Ro52+La+ autoantibody profile most closely matches for pSS. Further research is needed to find marker antibodies for SS and quantification methods. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this study was to determine the impact of the routine use of serum C‐peptide in an out‐patient clinic setting on individuals with a clinician‐diagnosis of type 1 diabetes. Methods: In this single‐centre study, individuals with type 1 diabetes of at least 3 years duration were offered random serum C‐peptide testing at routine clinic review. A C‐peptide ≥200 pmol/L prompted further evaluation of the individual using a diagnostic algorithm that included measurement of islet cell antibodies and genetic testing. Where appropriate, a trial of anti‐diabetic co‐therapies was considered. Results: Serum C‐peptide testing was performed in 859 individuals (90% of the eligible cohort), of whom 114 (13.2%) had C‐peptide ≥200 pmol/L. The cause of diabetes was reclassified in 58 individuals (6.8% of the tested cohort). The majority of reclassifications were to type 2 diabetes (44 individuals; 5.1%), with a smaller proportion of monogenic diabetes (14 individuals; 1.6%). Overall, 13 individuals (1.5%) successfully discontinued insulin, while a further 16 individuals (1.9%) had improved glycaemic control following the addition of co‐therapies. The estimated total cost of the testing programme was £23,262 (~€26,053), that is, £27 (~€30) per individual tested. In current terms, the cost of prior insulin therapy in the individuals with monogenic diabetes who successfully stopped insulin was approximately £57,000 (~€64,000). Conclusions/interpretation: Serum C‐peptide testing can easily be incorporated into an out‐patient clinic setting and could be a cost‐effective intervention. C‐peptide testing should be strongly considered in individuals with a clinician‐diagnosis of type 1 diabetes of at least 3 years duration. Click here to access the podcast for this paper. [ABSTRACT FROM AUTHOR]

• This paper provides a new theoretical framework from disease-related biomolecules to treatment progress. • This paper further collected evidence for the conclusion that psoriasis is an autoimmune disease. • This paper summarizes the development of biologic therapies for psoriasis and psoriatic arthritis. Over the past half century, psoriasis is considered as an immune-mediated inflammatory skin disease with the combined hallmarks of autoimmunity and autoinflammation, according to growing volumes of clinical and experimental findings. There is currently no cure for psoriasis, current treatment strategies focus on symptom control, disease minimization, and patient's quality of life enhancement. To meet these challenges, it keeps imperative to discover potential biomarkers, so that not only can they be used for the prediction and monitoring of psoriasis disease in clinic, but also can provide novel therapeutic targets or treatment strategies for psoriasis sufferers. This review systematically demonstrates the research progress of psoriasis-related biomarkers and elaborates their related mechanisms in the pathological development of psoriasis and psoriatic arthritis. In addition, we summarize the development of biologic therapies for psoriasis and psoriatic arthritis in order to drive the broader discussion of psoriasis as an autoimmune-mediated inflammatory skin disease. [ABSTRACT FROM AUTHOR]

Autoimmune antibody profiling plays a prominent role in both classification and prognosis of systemic sclerosis (SSc). In the last years novel autoantibodies have been discovered and have become available in diagnostic assays. However, standardization in autoimmune serology is lacking, which may have a negative impact on the added value of autoantibodies in diagnosis and prognosis of SSc. In this paper we describe the comparison of commercially available diagnostic assays for the detection of SSc-associated autoantibodies and explored the coexistence of multiple SSc-associated autoantibodies within patients. Serum samples of 347 patients from the Nijmegen Systemic Sclerosis Cohort were included in this study. All patients fulfilled the ACR/EULAR 2013 classification criteria for SSc and were classified as DcSSc or LcSSc according to the Leroy and Medsger criteria. All samples were evaluated on standard laboratory diagnostic tests for detection of SSc-specific autoantibodies CENPA and CENPB (ACA), Scl-70 (ATA), RNA Polymerase III (rp11/155) (ARA), and SSc-associated autoantibodies Fibrillarin, Th-To, PM-scl75, PM-Scl100, RNP68/A/C, Ku, NOR90, and PDGFR from suppliers EUROIMMUN, D-tek and Thermo Fisher Scientific. We found that 79% of the patients was positive for one or more of the SSc autoantibodies. Overall, a high agreement was observed between the diagnostic methods for the SSC-specific autoantibodies listed in the ACR/EULAR criteria (ATA, ACA, and ARA) (Cohen's kappa 0.53–0.97). However, a lower agreement was found for SSc-associated autoantibodies PM-Scl, and Ku, as well as for the SSc-specific autoantibodies fibrillarin and Th-To. Furthermore, the data revealed that the presence of ATA, ARA and ACA is predominantly mutually exclusive, with only a fraction of the patients testing positive for both ATA and ARA. Our data showed high concordance of prevalent SSc-specific autoantibodies between different diagnostic assays. Further standardisation for low prevalent SSc-specific and SSc-associated autoantibodies is needed. [ABSTRACT FROM AUTHOR]

Objective: Microwave ablation therapy has been attracting great attention due to its advantages such as low complication rate, good cosmetic results and effective nodule shrinking. Although the effect of thermal ablation therapy on the nodule volume reduction rate has been shown several studies, a limited number of papers have been reported for the effects of microwave ablation (MWA) on thyroid function tests. The aim of this study was to investigate the short‐ and long‐term effects of MWA therapy on thyroid function tests (TFTs), thyroglobulin (Tg) and thyroid autoantibodies in euthyroid patients. Design, patients and measurements: Demographic data of the patients, TFTs, Tg, thyroid autoantibodies and thyroid volume of the nodules were recorded before the procedure and follow‐up. Any differences in serum thyroid hormone levels were investigated in pre‐, post‐ and 6‐month follow‐up periods before and after MWA. Results: The difference between all thyroid hormone levels at pre MWA and 24 h after MWA was statistically significant (p <.001). FT3 (4.62) pmol/L and FT4 (10.81) pmol/L median levels increased significantly (p <.001), while thyrotropin (TSH) levels decreased at 24 h after MWA (p <.001). Thyroid antibodies levels were not statistically different at 6‐month (p >.05), whereas Tg levels decreased (p <.001) compared to pre MWA. Conclusions: While no significant effect was observed at 6 month, the effect of MWA on thyroid function tests was prominent at 24 h. [ABSTRACT FROM AUTHOR]

The immune system employs complex tolerance mechanisms in order to avoid harmful autoimmunity, yet autoantibodies are frequently observed in cancer. In a paper in Cell , Mazor et al. report that autoantibodies produced by tumor-infiltrating B cells in human ovarian cancer frequently recognize the self-protein matrix metalloproteinase 14 (MMP14) through two distinct mechanisms of tolerance disruption. [ABSTRACT FROM AUTHOR]

Recurrent spontaneous abortion (RSA) generally refers to 3 or more consecutive miscarriages with same-sex couples before 20 weeks of gestation. The cause of RSA is still unknown, immune-related factor could be an important cause. Those factors of immune abnormality are not only related to the changes of maternal autoimmune, but also related to the imbalance of maternal -fetal immune tolerance. Further studies on RSA immune -related factors are of great significance for exploring new treatment methods of RSA and improving pregnancy outcomes in RSA patients. In this paper, the immune-related factors and progress of RSA are reviewed in order to provide new ideas for the diagnosis and treatment of RSA. [ABSTRACT FROM AUTHOR]

Angiotensin II Type 1 Receptor Autoantibodies (AT1-AA) as a functional receptor activator can persistently activate Angiotensin II Type 1 Receptor (AT1R) by causing AT1R non-desensitization which is one of the important pathogenesis of preeclampsia (PE). However, the molecular mechanisms of AT1-AA results AT1R non-desensitization remain unknown. In order to explore the background molecular mechanisms of AT1R non-desensitization induced by AT1-AA, we construct dynamical models which are composed of control model (based on the body of healthy pregnant women) and experimental group models (based on the body of pregnant women with PE) in this paper. We also consider the effect of membrane fluidity on the reaction when building the dynamical models. In the experiment group models, we establish two models that caused AT1R non-desensitization: endocytosis disorder model and conformational change model. We write C++ and MATLAB programs to do the data fitting. By comparing the data fitting results and analyzing the images of models and corresponding Bayesian information criterion (BIC) values, we conclude that conformational changes may be the key molecular mechanism of AT1R non-desensitization. [ABSTRACT FROM AUTHOR]