Search

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]

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]

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]

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]

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]

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]

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]

Maturity onset diabetes of the young (MODY) is a highly heterogeneous monogenic disease that occurs due to β‐cell dysfunction. It is divided into different types depending on the gene mutated, and a total of 16 genes have been found to be associated with MODY. However, due to the current lack of understanding of monogenic diabetes, 90% of MODY is currently misdiagnosed and ignored in clinical practice. In this paper, we report the clinical data of a patient diagnosed with diabetes. Genetic testing revealed a novel BLK heterozygous mutation (c.363G>A) in the patient and in his father and son. He had no islet‐specific autoantibodies and showed a reduced meal‐induced response of insulin. Precise diagnosis of MODY individuals is important to the treatment. [ABSTRACT FROM AUTHOR]

Autoantibodies are immune system‐produced antibodies that wrongly target the body's cells and tissues for attack. The COVID‐19 pandemic has made it possible to link autoantibodies to both the severity of pathogenic infection and the emergence of several autoimmune diseases after recovery from the infection. An overview of autoimmune disorders and the function of autoantibodies in COVID‐19 and other infectious diseases are discussed in this review article. We also investigated the different categories of autoantibodies found in COVID‐19 and other infectious diseases including the potential pathways by which they contribute to the severity of the illness. Additionally, it also highlights the probable connection between vaccine‐induced autoantibodies and their adverse outcomes. The review also discusses the therapeutic perspectives of autoantibodies. This paper advances our knowledge about the intricate interaction between autoantibodies and COVID‐19 by thoroughly assessing the most recent findings. [ABSTRACT FROM AUTHOR]

Accumulating evidence shows that SARS‐CoV‐2 can potentially trigger autoimmune processes, which can be responsible for the long‐term consequences of COVID‐19. Therefore, this paper aims to review the autoantibodies reported in COVID‐19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G‐protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS‐CoV‐2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically‐relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS‐CoV‐2 infection or the accidental post‐COVID‐19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post‐COVID‐19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age‐ and sex‐related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS‐CoV‐2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS‐CoV‐2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID‐19 convalescents. [ABSTRACT FROM AUTHOR]

This article focuses on the cigarette paper atrophy. This is an uncommon disease of unknown etiology. Recent studies have confirmed a significant increase of organ-specific autoantibodies in patients with lichen sclerosis et atrophiens (LSA). In the native African population LSA has been considered rare. Five patients are believed to be reported from West Africa. The disease is seen in children as well as in adults, and it occurs 10 times more frequently in women than in men, occuring around and after menopause. The anogenital region is involved in most cases. Nongenital lesions are symptomless and occur mostly on the trunk. The lesions start as small shiny ivory white papules that later coalesce to form well-demarcated plaques.

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]

Abstract: Large-scale programs designed to assess risk for type 1 dia-betes through serologic assessment of autoantibodies to recombinant b-cell autoantigens are hampered by several limitations, including the methods for sample collection and assay performance, as well as the volume required for autoantibody determinations. The present study was designed to develop a low sample-volume, primary screening method for autoantibody detection of high specificity and sensitivity, and to determine the feasibility of dried blood spots collected on filter paper in serving as vehicles for such determinations. Autoantibodies to glutamic acid decarboxylase (GAD) and ICA512bdc (IA-2), both indi-vidually and in combination, were determined in persons with type 1 diabetes, healthy controls, or individuals with other autoimmune disor-ders. Autoantibody results for serum, plasma, and dried blood spots were compared. GAD, IA-2, and combined GAD:IA-2 autoantibodies were concordant in their measurement from minimal volumes of serum, plasma, and whole blood extracted from dried filter paper. The autoan-tibody levels from the dried blood spots were, however, lower than corresponding serum samples, and, as currently designed, failed to de-tect low-titer autoantibodies. Despite this limitation, screening for dia-betes risk can be performed using small volumes of whole blood, serum, or plasma collected onto filter paper. These methodological im-provements should simplify matters, reduce costs, and increase the effi-cacy of screening programs for type 1 diabetes. Further development of better substrates:methods for blood-specimen collection seems necessary to exploit the full potential of this and other autoantibody measure-ment strategies for screening large populations. [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]

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 association between alopecia areata (AA) and autoimmune thyroid diseases (AITD) has been suggested; however, the chronological relationship between AA and AITD remains elusive. A systematic review and meta-analysis were conducted to assess the association between AA and AITD focusing on the prevalence of thyroid antibodies, thyroid diseases and serological thyroid dysfunctions, respectively. Data collection was performed in October 2018 by searching for articles in two electronic databases: Medline and Embase. Case-control, cohort and cross-sectional studies were included. Meta-analysis of studies eligible for quantitative synthesis was performed to estimate pooled odds ratios of thyroid antibodies; thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab), diagnosed thyroid diseases and serological thyroid dysfunctions. Four hundred and eighty nine research papers were identified and 17 studies with 262 581 patients and 1 302 655 control subjects were included for quantitative synthesis. AA was significantly associated with both TPO-Ab and TG-Ab. In comparison, there was no significant association between AA and diagnosed hypothyroidism or hyperthyroidism and serological hypothyroidism or hyperthyroidism. In conclusion, AA is significantly associated with the existence of thyroid antibodies rather than with clinical or laboratory thyroid abnormality. Lack of long-term follow-up data is a limitation of the existing published work. Our findings do not support routine screening of thyroid diseases for asymptomatic AA patients but highlight the potential future risk of AITD particularly in severe and refractory AA., (© 2019 Japanese Dermatological Association.)

The aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population. WHAT THIS PAPER ADDS: Rituximab appears to control disease in most anti-myelin oligodendrocyte glycoprotein-positive patients with relapsing neuroinflammatory disease. Rituximab was associated with transitory, mild-to-moderate infusion-related effects. Half of patients treated with rituximab developed leukopenia or hypogammaglobulinemia. No opportunistic infections were observed. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune inflammatory disease characterized by the production of numerous autoantibodies and cytokines, as well as multiple organ damage. Specific B cell subsets negatively regulate immune responses and have been termed regulatory B cells (Bregs). Bregs are characterized by the production of the immunoregulatory cytokines interleukin (IL)-10, IL-35, and transforming growth factor (TGF)-β. Bregs suppress other immune cells through the secretion of these immunosuppressive cytokines and have thus been studied extensively for their potential role in the treatment of various autoimmune diseases. The progress of the research on Bregs and SLE in recent years is reviewed in this paper. [ABSTRACT FROM AUTHOR]

In a rare neurologic disease known as IgM monoclonal gammopathy the immune system targets a sulfated trisaccharide known as the Human Natural Killer‐1 (HNK‐1) epitope that comprises a constituent of the myelin sheath known as MAG (myelin‐associated glycoprotein). This Editorial highlights a study by Aliu and colleagues in the current issue of the Journal of Neurochemistry, in which the investigators constructed a biodegradable poly‐l‐lysine backbone with multiple copies of this sulfated HNK‐1 trisaccharide. This decoy, poly(phenyl disodium 3‐O‐sulfo‐β‐d‐glucopyranuronate)‐(1→3)‐β‐d‐galactopyranoside, known as PPSGG, removed anti‐MAG IgM autoantibodies from the blood, while not activating the immune system. These findings provide a path for the selective removal of a pathogenic set of antibodies that target the myelin sheath resulting in neuropathy. These findings are applicable to a parallel strategy for the generation of polysaccharides similar to those present in the receptor‐binding domain of CoViD‐19, which might inhibit viral adhesion to its receptor, the angiotensin‐converting enzyme‐2 (ACE2) protein, thereby impairing cellular uptake of the virus itself. The deployment of complex polysaccharides that mimic actual COVID19 polysaccharides on the spike protein may also provide a feasible structural basis for a vaccine. Carbohydrate mimics, if conjugated to a carrier or backbone, might provoke an immune response to the spike protein. A vaccine that targets critical carbohydrates on COVID19, and then neutralizes the virus would recapitulate a successful strategy employed in other microbial vaccines, like the pneumococcal vaccines and the meningococcal vaccines. These vaccines direct an immune response to complex carbohydrates and successfully prevent life‐threatening disease. This paper provides lessons from a rare neurologic disease that may teach us strategies applicable to a global pandemic. [ABSTRACT FROM AUTHOR]

Females with myasthenia gravis (MG) worry about their disease having negative consequences for their children. Autoimmune disease mechanisms, treatment and heredity could all have an impact on the child. This is a subject review where Web of Science was searched for relevant keywords and combinations. Controlled and prospective studies were included, and also results from selected and unselected patient cohorts, guidelines, consensus papers and reviews. Neonatal MG with temporary muscle weakness occurs in 10% of newborn babies where the mother has MG, due to transplacental transfer of antibodies against acetylcholine receptor (AChR), muscle‐specific kinase (MuSK) or lipoprotein receptor‐related protein 4 (LRP4). Arthrogryposis and fetal AChR inactivation syndrome with contractures and permanent myopathy are rare events caused by mother's antibodies against fetal type AChR. The MG drugs pyridostigmine, prednisolone and azathioprine are regarded as safe during pregnancy and breastfeeding. Methotrexate, mycophenolate mofetil and cyclophosphamide are teratogenic. Mother's MG implies at least a 10‐fold increased risk for MG and other autoimmune diseases in the child. MG females should receive specific information about pregnancy and giving birth. First‐line MG treatments should usually be continued during pregnancy. Intravenous immunoglobulin and plasma exchange represent safe treatments for exacerbations. Neonatal MG risk means that MG women should give birth at hospitals experienced in neonatal intensive care. Neonatal MG needs supportive care, rarely also acetylcholine esterase inhibition or intravenous immunoglobulin. Women with MG should be supported in their wish to have children. [ABSTRACT FROM AUTHOR]

The aim of the present review is to provide an update of the current research into the pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype. This is a common Caucasoid haplotype carried by most people who type for HLA‐B8, DR3. Numerous genetic studies reported that individuals with certain HLA alleles have a higher risk of specific autoimmune disorders than those without these alleles. However, much remains to be learned about the heritability of autoimmune conditions. Recently, progress and advances in the field of genome‐wide‐association studies have revolutionized the capacity to perform large, economically feasible, and statistically robust analyses of HLA within 8.1 ancestral haplotype, and understand its contribute to autoimmune events. In this paper, the characteristic features of this haplotype that might give rise to diverse autoimmune phenotypes are reviewed, focusing on the contribution of the HLA‐DRB1 gene, the most polymorphic sequence within the HLA II region. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Key Clinical Message: Adult‐onset immunodeficiency (AOID) is an emerging acquired immunodeficiency, characterized by multiple opportunistic infections including non‐tuberculous mycobacterium (NTM) due to the presence of anti‐IFN‐γ autoantibody (AIGA). This case highlights the challenges of accurate diagnosis of monoclonal gammaglobulinemia with NTM infection and favorable outcomes of anti‐plasma cell therapy in AOID. Adult‐onset immunodeficiency (AOID) is an emerging acquired immunodeficiency due to anti‐IFN‐γ autoantibody (AIGA) with low morbidity, frequent disseminated infections, a prolonged course, difficult diagnosis and treatment, and a poor prognosis. Here, we report a patient with positive AIGA and monoclonal gammaglobulinemia who was mimicking symptomatic multiple myeloma and resulting in a non‐tuberculous mycobacterial (NTM) infection. While he achieved an excellent therapeutic effect with anti‐plasma cell therapy, it also serves as a warning that monoclonal gammaglobulinemia with NTM infection is easily misdiagnosed as symptomatic multiple myeloma, and the screening for AIGA should not be ignored in patients with NTM infection. [ABSTRACT FROM AUTHOR]

Background: Autoantibody biomarkers are valuable tools used to diagnose and manage autoimmune diseases in dogs. However, prior publications have raised concerns over a lack of standardization and sufficient validation for the use of biomarkers in veterinary medicine. Objectives: Systematically compile primary research on autoantibody biomarkers for autoimmune disease in dogs, summarize their methodological features, and evaluate their quality; synthesize data supporting their use into a resource for veterinarians and researchers. Animals: Not used. Methods: Five indices were searched to identify studies for evaluation: PubMed, CAB Abstracts, Web of Science, Agricola, and SCOPUS. Two independent reviewers (AET and ELC) screened titles and abstracts for exclusion criteria followed by full‐text review of remaining articles. Relevant studies were classified based on study objectives (biomarker, epitope, technique). Data on study characteristics and outcomes were synthesized in independent data tables for each classification. Results: Ninety‐two studies qualified for final analysis (n = 49 biomarker, n = 9 epitope, and n = 34 technique studies). A high degree of heterogeneity in study characteristics and outcomes reporting was observed. Opportunities to strengthen future studies could include: (1) routine use of negative controls, (2) power analyses to inform sample sizes, (3) statistical analyses when appropriate, and (4) multiple detection techniques to confirm results. Conclusions: These findings provide a resource that will allow veterinary clinicians to efficiently evaluate the evidence supporting the use of autoantibody biomarkers, along with the varied methodological approaches used in their development. [ABSTRACT FROM AUTHOR]

Researchers have identified a new monogenic form of systemic lupus erythematosus caused by mutations that result in increased Toll-like receptor 7 (TLR7) signaling. This provides further evidence for the critical role of dysregulated Toll-like receptor 7 (TLR7) signaling in inappropriate activation of self-reactive B cells and autoantibody production. To determine whether mutations in I TLR7 i were able to drive autoantibody production, Brown I et al i .2 generated a mouse model of the Y264H mutation found in the initial patient. [Extracted from the article]

Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non‐invasive source for disease diagnosis through liquid biopsy. In this investigation, we introduce a streamlined and effective approach for the capture and quantitative assessment of migrasomes, employing wheat germ agglutinin (WGA)‐coated magnetic beads and flow cytometry (referred to as WBFC). Subsequently, we examined the levels of migrasomes in the urine of kidney disease (KD) patients with podocyte injury and healthy volunteers using WBFC. The outcomes unveiled a substantial increase in urinary podocyte‐derived migrasome concentrations among individuals with KD with podocyte injury compared to the healthy counterparts. Notably, the urinary podocyte‐derived migrasomes were found to express an abundant quantity of phospholipase A2 receptor (PLA2R) proteins. The presence of PLA2R proteins in these migrasomes holds promise for serving as a natural antigen for the quantification of autoantibodies against PLA2R in the serum of patients afflicted by membranous nephropathy. Consequently, our study not only pioneers a novel technique for the isolation and quantification of migrasomes but also underscores the potential of urinary migrasomes as a promising biomarker for the early diagnosis of KD with podocyte injury. [ABSTRACT FROM AUTHOR]

Despite being some of the most anecdotally well‐known roads to pathogenesis, the mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation of the cellular immune system and the characteristic development of autoantibodies have been linked to oxidative stress. Typical clinical manifestations, such as joint swelling and deformities and inflammation of the skin and internal organs, have also been connected directly or indirectly to redox mechanisms. The differences in generation and restraint of oxidative stress provide compelling evidence for the broad variety in pathology among rheumatic diseases and explain some of the common triggers and discordant manifestations in these diseases. Growing evidence of redox mechanisms in pathogenesis has provided a broad array of new potential therapeutic targets. Here, we explore the mechanisms by which oxidative stress is generated, explore its roles in autoimmunity and end‐organ damage, and discuss how individual rheumatic diseases exhibit unique features that offer targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editors discuss various reports within the issue on topics including the aspects of serum autoantibody research, the up-to-date overview of Alkalides system and the relevance of autoantibodies in autoimmune gastrointestinal and liver diseases.

The article presents information about abstracts of various papers that will be discussed at the Platform Session of the 6th European Congress on Epileptology that will be held on June 2, 2004. One of the papers that will be discussed is "Analysis of Autoantibodies (AAB) Against Human Brain AMPA Receptor in a Patient With Partial Epilepsy," by I.Y. Kovaleva. The changing of the level of AAB to AMPA receptors can be recommended as a tool for monitoring treatment and for the prediction of treatment outcome. Other papers that will be discussed are "Extrapyramidal Motor Symptoms in Focal Seizures," by E. Trinka and "Expression and Functional Significance of MDR1 Expression in a Chronic Model of Limbic Seizures," by N. Marchi.

Antibody eradication is the ultimate goal of inhibitor management. The only clinically proven strategy for achieving antigen-specific tolerance to factor VIII is immune tolerance induction (ITI). Our knowledge about ITI in haemophilia A and B was, historically, derived from small cohort studies and retrospective national and international ITI registries. Practice is now further influenced by prospective cohort data, and the results of a single prospective randomized international ITI trial. However, due to the low incidence of inhibitors in haemophilia B, there are few comparable data from which to develop a useful evidence-based approach to the prevention and eradication of factor IX inhibitors. The lack of an effective strategy is particularly problematic given the morbidity associated with the unique occurrence of allergic and anaphylactic reactions that often herald factor IX antibody development and preclude effective eradication. This paper will discuss our current understanding of immune tolerance outcome and outcome predictors for haemophilia A and B; review the current consensus practice recommendations for ITI; and summarize the emerging body of immunological science relating to antibody formation and tolerance. It will conclude by suggesting how our knowledge might inform the future investigative priorities impacting the therapeutic and preventative tolerance strategies of tomorrow., (© 2012 Blackwell Publishing Ltd.)

In this paper, we demonstrate that circulating antibodies from chronic periodontitis patients reacting with atrial β(1)-adrenoceptors (β(1)-ARs) act as an inducer of soluble CD40 ligand (sCD40L) release and prostaglandin E(2) (PGE(2)) generation. By enzyme-linked immunosorbent assay using β(1) synthetic peptide (with an amino acid sequence identical to the second loop of human myocardial β(1)-ARs) as a coating antigen, we demonstrated reactivity against the second extracellular loop on human myocardial β(1)-ARs. This autoantibody present in the serum of chronic periodontitis patients was significantly correlated with the release of sCD40L and PGE(2). The release of sCD40L was blunted by atenolol, SP600125 and β(1) synthetic peptide, and PGE(2) generation was inhibited by DuP 697 and slightly by FR122049. The effects of the antibody incubated with isolated rat atria upregulated sCD40L release with an increase of PGE(2) production and c-Jun N-terminal kinase phosphorylation. These results indicate that in chronic periodontitis patients, there is a positive association between sCD40L release and PGE(2) generation via the action of β(1)-AR antibodies.

C1q nephropathy is a rare glomerular disease with characteristic mesangial C1q deposition noted on immunofluorescence microscopy. It is histologically defined and poorly understood. Light microscopic features are heterogeneous and comprise minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and proliferative glomerulonephritis. Clinical presentation is also diverse, and ranges from asymptomatic hematuria or proteinuria to frank nephritic or nephrotic syndrome in both children and adults. Hypertension and renal insufficiency at the time of diagnosis are common findings. Optimal treatment is not clear and is usually guided by the underlying light microscopic lesion. Corticosteroids are the mainstay of treatment, with immunosuppressive agents reserved for steroid resistant cases. The presence of nephrotic syndrome and FSGS appear to predict adverse outcomes as opposed to favorable outcomes in those with MCD. Further research is needed to establish C1q nephropathy as a universally recognized distinct clinical entity. In this paper, we discuss the current understanding of pathogenesis, histopathology, clinical features, therapeutic options, and outcomes of C1q nephropathy. [ABSTRACT FROM AUTHOR]

Background/aim: Pegylated interferon (Peg-IFN) plus ribavirin is the standard therapy for hepatitis C. Peg-IFN has several antiviral mechanisms, but its role in hepatitis C treatment seems to be related to its immunomodulatory effect. Ribavirin, an antiviral agent, potentiates IFN activity when added to it. Both drugs are associated with adverse reactions of different magnitudes. Autoimmune phenomena have been reported with this treatment. In this paper, we describe cases of ALT/GGT flares during Peg-IFN plus ribavirin treatment, which related to the appearance of anti-Golgi antibody and disease progress., Methods: We investigated three patients with hepatitis C and severe ALT/GGT flares during Peg-IFN and ribavirin treatment coinciding with anti-Golgi complex antibody as the only marker of autoimmunity. We then reviewed the medical files and tested anti-Golgi antibody in stored sera from 25 patients treated with conventional IFN and in 14 patients treated with Peg-IFN., Results: The three patients were male, over 45 years of age; all were relapsers and non-responders. Anti-Golgi antibody was positive during treatment coinciding with ALT/GGT flares but with hepatitis C virus (HCV)-RNA negativity, disappearing after stopping treatment, with normalization of ALT/AST levels. One patient had progression of fibrosis from F2 to F3 despite negativity of HCV-RNA. In the last group, only two patients treated with Peg-IFN experienced ALT/GGT flares but without anti-Golgi antibody, Conclusions: The presence of anti-Golgi complex antibody could be a marker of a temporary autoimmune phenomenon and progressive disease.

Background: Antibodies against tRNP((ser)sec) (ribonucleoproteins, RNP) have been described in our laboratory as markers of poor outcome in type 1 autoimmune hepatitis (AIH). The antigenic protein has been sequenced and cloned as a 48.8 kDa protein and identified with soluble liver antigen (SLA) and liver-pancreas (LP) antigen. The aim of this paper was to determine the best assay by which to detect these antibodies in type 1 AIH., Methods: A simple and reliable enzyme linked immunoassay based on prokaryotically expressed protein was compared with an immunoblot assay using prokaryotically- and eukaryotically-expressed proteins and an assay based on immunoprecipitated RNAs from HeLa cell extracts. Eighty-one sera from 58 patients with type 1 AIH, 168 sera from patients with autoimmune diseases or chronic hepatitis C, and 60 sera from healthy subjects were similarly tested., Results: The specificity of the assays was 100%, but the frequency of seropositivity was higher in the assay based on immunoprecipitated RNAs (44.4%) than in the enzyme-linked immunosorbent assay (ELISA) (16%) and the immunoblot assay with prokaryotically (12.34%) and eukaryotically (14.8%)-expressed protein. There were no clinical differences between the patients positive by ELISA, immunoblot assay, or immunoprecipitated RNAs., Conclusions: These results suggest that the analysis of the immunoprecipitated RNAs is the most useful, sensitive and specific method to detect anti-tRNP((ser)sec)/SLA/LP autoantibodies., (Copyright Blackwell Munksgaard 2005)

Introduction. Liver involvement due to hyperthyroidism and also ANCA positive vasculitis related renal failure cases were reported separately several times before. However, to our knowledge, these two complications together in the same case had never been observed before. Case Presentation. The case of an ANCA positive 71-year-old Caucasian male with renal failure and lung involvement, subclinical hyperthyroidism, and intrahepatic cholestatic jaundice was presented in this paper. After exclusion of all of the other possibilities, cholestatic hepatitis was explained by subclinical hyperthyroidism; renal failure and lung involvement were interpreted as ANCA related vasculitis which might be a side effect of propylthiouracil use. Conclusion. The coexistence of these rare conditions in the same patient deserves emphasis and it is worth reporting. This case demonstrates that following the clinical course of the patient is essential after prescribing any medications to see whether any complication occurs or not. If the complications of this case were noticed earlier, it would be possible to treat and to prevent the permanent damages. [ABSTRACT FROM AUTHOR]

γδ T cells are a minor population of T cells that express the TCR γδ chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, γδ T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on γδ T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of γδ T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of γδ T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of γδ T-cell-targeted therapy. [ABSTRACT FROM AUTHOR]

Epitopes recognized by factor VIII (FVIII) inhibitors of Chinese origin were analysed by immunoblotting with full-length recombinant FVIII (rFVIII), thrombin-activated FVIII (FVIIIa) and 16 FVIII fusion proteins synthesized by bacteria. Twenty-eight patients, 12 with haemophilia A and 16 with autoimmune diseases, were recruited. Antibodies from 22 patients showed reactivity with rFVIII, 20 with FVIIIa, and one reacted only with FVIII fusion proteins. Of these 22 cases, most were reactive with A2-a2 and A3-C1-C2 of FVIII(a). Of the nine cases that depicted binding to the fusion proteins, three were reactive with the A domains, three with only the B domain, and the other three with both the A and B (or C) domains. An epitope for a neutralizing antibody of a haemophilia A patient, designated TWN-112, was localized to residues 323-390, specified by FVIII fusion proteins. The same epitope also appeared on an FVIII-expression phage library screening. Immunoabsorption of antibodies from TWN-112 with the epitope reduced the neutralizing activity of the inhibitor by 33%. The incidence of a1 of FVIII is higher, and that of a3 is lower, than previously reported. Two novel epitopes, reported for the first time in this paper, were localized on the 8B2 (amino acid residues 1022-1204) and 8A2(V) (residues 673-740) fusion proteins. These two epitopes were able to reduce inhibitory antibody activity by 24% and 25% respectively. Changes of FVIII fragment specificity were also observed in one of six patients for whom multiple samples, collected at different times, were available. Our initial finding showed that the FVIII inhibitors in these Chinese patients shared epitopes with those of patients from very different genetic backgrounds, suggesting a common mechanism for the development of FVIII inhibitors.

Senear-Usher syndrome or pemphigus erythematosus is a pathology that overlaps clinically and serologically with pemphigus foliaceus and lupus erythematosus. Skin biopsies of patients with pemphigus erythematosus reveal acantholysis and deposits of immunoglobulins in desmosomes, and they are positive in the lupus band test. In the present paper, we determined whether the autoantibodies associated with pemphigus erythematosus targeted a single antigen or multiple antigens as a result of the stimulation of independent B cell clones. Our present paper demonstrates that patients with pemphigus erythematosus produce both antiepithelial antibodies specific for desmoglein 1 and 3 and antinuclear antibodies specific for Ro, La, Sm, and double-stranded DNA antigens. After eluting specific anti-epithelial or anti-nuclear antibodies, which were recovered and tested using double-fluorescence assays, a lack of cross-reactivity was demonstrated between desmosomes and nuclear and cytoplasmic lupus antigens. This result suggests that autoantibodies in pemphigus erythematosus are directed against different antigens and that these autoantibodies are produced by independent clones. Given these clinical and serological data, we suggest that pemphigus erythematosus behaves as a multiple autoimmune disease. [ABSTRACT FROM AUTHOR]

The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell mediated. This new understanding of the role of B cells opened up novel therapeutic options for the treatment of autoimmune diseases. This paper includes an overview of the different functions of B cells in autoimmunity; the involvement of B cells in systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes; and current B-cell-based therapeutic treatments. We conclude with a discussion of novel therapies aimed at the selective targeting of pathogenic B cells. [ABSTRACT FROM AUTHOR]

Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple genetic risk factors, high levels of interferon alpha (IFN-α), and the production of autoantibodies against components of the cell nucleus. Interferon regulatory factor 5 (IRF5) is a transcription factor which induces the transcription of IFN-α and other cytokines, and genetic variants of IRF5 have been strongly linked to SLE pathogenesis. IRF5 functions downstream of Toll-like receptors and other microbial pattern-recognition receptors, and immune complexes made up of SLE-associated autoantibodies seem to function as a chronic endogenous stimulus to this pathway. In this paper, we discuss the physiologic role of IRF5 in immune defense and the ways in which IRF5 variants may contribute to the pathogenesis of human SLE. Recent data regarding the role of IRF5 in both serologic autoimmunity and the overproduction of IFN-α in human SLE are summarized. These data support a model in which SLErisk variants of IRF5 participate in a "feed-forward" mechanism, predisposing to SLE-associated autoantibody formation, and subsequently facilitating IFN-α production downstream of Toll-like receptors stimulated by immune complexes composed of these autoantibodies. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies against nuclear antigens and a systemic inflammation that can damage a broad spectrumof organs. SLE patients suffer from a wide variety of symptoms, which can affect virtually almost any tissue. As lupus is difficult to diagnose, the worldwide prevalence of SLE can only be roughly estimated to range from 10 and 200 cases per 100,000 individuals with dramatic differences depending on gender, ethnicity, and location. Although the treatment of this disease has been significantly ameliorated by new therapies, improved conventional drug therapy options, and a trained expert eye, the underlying pathogenesis of lupus still remain widely unknown. The complex etiology reflects the complex genetic background of the disease, which is also not well understood yet. However, in the past few years advances in lupus genetics have been made, notably with the publication of genome-wide association studies (GWAS) in humans and the identification of susceptibility genes and loci in mice. This paper reviews the role of MHC-linked susceptibility genes in the pathogenesis of systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

Anti-Ro/SSA antibodies are among the most frequently detected autoantibodies against extractable nuclear antigens and have been associated with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Although the presence of these autoantibodies is one of the criteria for the diagnosis and classification of SS, they are also sometimes seen in other systemic autoimmune diseases. In the last few decades, the knowledge of the prevalence of anti-Ro/SSA antibodies in various autoimmune diseases and symptoms has been expanded, and the clinical importance of these antibodies is increasing. Nonetheless, the pathological role of the antibodies is still poorly understood. In this paper, we summarize the milestones of the anti-Ro/SSA autoantibody system and provide new insights into the association between the autoantibodies and the pathogenesis of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multisystem disease characterized by B cells producing autoantibodies against nuclear proteins and DNA, especially anti-double-strand DNA (dsDNA) antibodies. RP105 (CD180), the toll-like receptor- (TLR-) associated molecule, is expressed on normal B cells. However, RP105-negative B cells increase in peripheral blood from patients with active SLE. RP105 may regulate B-cell activation, and RP105-negative B cells produce autoantibodies and take part in pathophysiology of SLE. It is possible that targeting RP105-negative B cells is one of the treatments of SLE. In this paper, we discuss the RP105 biology and clinical significance in SLE. [ABSTRACT FROM AUTHOR]