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]

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]

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]

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 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]

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]

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]

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]

Aim: To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease.Method: In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively.Results: Of the 31 children studied, 14 presented with acute disseminated encephalomyelitis (ADEM); they were younger (mean 4.1y) than the remainder (mean 8.5y) who presented with optic neuritis and/or transverse myelitis (p<0.001). Similarly, children who had an abnormal brain magnetic resonance imaging (MRI) at onset (n=20) were younger than patients with normal MRI at onset (p=0.001) or at follow-up (p<0.001). 'Leukodystrophy-like' MRI patterns of confluent largely symmetrical lesions was seen during the course of the disease in 7 out of 14 children with a diagnosis of ADEM, and was only seen in children younger than 7 years of age. Their disability after a 3-year follow-up was mild to moderate, and most patients continued to relapse, despite disease-modifying treatments.Interpretation: MOG antibody should be tested in children presenting with relapsing neurological disorders associated with confluent, bilateral white matter changes, and distinct enhancement pattern. Children with MOG antibody-associated disease present with age-related differences in phenotypes, with a severe leukoencephalopathy phenotype in the very young and normal intracranial MRI in the older children. This finding suggests a susceptibility of the very young and myelinating brain to MOG antibody-mediated mechanisms of damage.What This Paper Adds: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination manifest with an age-related phenotype. Children with MOG antibody and 'leukodystrophy-like' imaging patterns tend to have poor response to second-line immunotherapy. [ABSTRACT FROM AUTHOR]

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.

The article presents abstracts of several papers related to autoantibodies including "DNAse serum and IgG activity in patients with early rheumatoid arthritis," by M. Volkava and A. Kundzer, "Alterations of the serum anti-MCV titer before and after the treatment of rheumatoid arthritis and its relation to disease activity (DAS28)," by M. Salesi, and "Activity of galactosidases in rheumatoid arthritis: a potential mechanism of agalactosylation of IgG," by C. Xu and colleagues.

lthough the majority of patients with CIDP variably respond to intravenous immunoglobulin (IVIg), steroids, or plasmapheresis, 30% of them are unresponsive or insufficiently responsive to these therapies. The heterogeneity in therapeutic responses necessitates the need to search for biomarkers to determine the most suitable therapy from the outset and explore the best means for monitoring disease activity. The ICE study, which led to the first FDA-approved indication for IVIg in CIDP, has shown that maintenance therapy prevents relapses and axonal loss. In this paper, the multiple actions exerted by IVIg on the immunoregulatory network of CIDP are discussed as potential predictors of response to therapies. Emerging molecular markers, promising in identifying responders to IVIg from non-responders, include modulation of Fc γRIIB receptors on monocytes and genome-wide transcription studies related to inflammatory mediators, demyelination, or axonal degeneration. Skin biopsies, Peripheral Blood Lymhocytes, CSF, and sera are accessible surrogate tissues for further exploring these molecules during therapies. [ABSTRACT FROM AUTHOR]

Please cite this paper as: IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis. Experimental Dermatology 2010; 19: 648-653. Background: Patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigoid gestationis (PG) have IgG antibodies against BP180 and BP230, components of the hemidesmosomes. Patients with linear IgA bullous dermatosis (LABD) have IgA autoantibodies against a 97/120-kDa protein which is highly homologous to a shedded fragment of the BP180-ectodomain. Objectives: The aim of our study was to determine the incidence of IgA autoantibodies directed against BP180/BP230 in the pemphigoids and LABD and to determine the antigenic regions that are targeted by IgA autoantibodies. Methods: Utilizing baculovirus-expressed recombinant BP180 and BP230 proteins, we performed immunoblot analyses for IgA reactivity of sera from patients with BP ( n = 30), MMP ( n = 10), PG ( n = 6), LABD ( n = 6) and from control patients with non-related pruritic dermatoses ( n = 8). Results: IgA reactivity against BP180 and/or BP230 was detected in 19/30 of the BP, in 7/10 of the MMP, in 6/6 of the LABD and in 3/6 of the PG sera, respectively, but not in the control group. In all subgroups, the major antigenic site recognized by IgA antibodies was located within the NH2-terminus of the BP180-ectodomain, but only a minority of the sera showed also IgA reactivity against the BP180-NC16a-domain. IgA reactivity against the central domain of BP180 was more frequently seen than against its COOH-terminus. IgA against the COOH- and NH2-terminus of BP230, respectively, was detected in 6/30 of the BP, 1/10 of the MMP, 1/6 of the LABD and 0/8 control sera. Conclusion: IgA reactivity against BP180 and/or BP230 is a common finding in the pemphigoids. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients. Experimental Dermatology 2010; 19: 458–463. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are intraepidermal blistering skin diseases. PV is characterised by autoantibodies directed against desmoglein (Dsg) 3 and in patients with the mucocutaneous variant also against Dsg 1, whereas in PF, only Dsg 1 is targeted. Here, ectodomains of Dsg 3 and Dsg 1 were recombinantly expressed in a human cell line (HEK293) and applied as authentic solid phases in ELISA test systems. Autoantibodies against Dsg 3 and/or Dsg 1 could be detected in 71 (100%) of 71 PV sera and against Dsg 1 in 48 (96%) of 50 PF sera. Control sera showed reactivity with Dsg 3 and Dsg 1 in 0.2% and 0.7%, respectively, of 401 healthy blood donors and in 2.1% of 48 randomly selected patients with bullous pemphigoid. No reactivity with Dsg 1 and 3 was detected in 21 patients with linear IgA disease. For both pemphigus variants, a statistically significant correlation between clinical severity and autoantibody levels was observed as demonstrated for 10 PV and 5 PF patients. In conclusion, the use of the ectodomains of Dsg 3 and 1 as target antigens expressed in a human cell line resulted in sensitive and specific ELISA systems for both diagnosis and monitoring of PV and PF. [ABSTRACT FROM AUTHOR]

The detection of autoantibodies is an important element in the diagnosis and monitoring of disease progression in patients with autoimmune diseases. In laboratory diagnostic tests for connective tissue and autoimmune liver diseases, indirect immunofluorescence on HEp-2 cells plays a central role in a multistage diagnostic process. Despite the high quality of diagnostics, findings at different laboratories can differ considerably due to a lack of standardization, as well as subjective factors. The present paper formulates recommendations for the standardized processing and interpretation of the HEp-2 cell test for the detection of non-organ-specific (especially antinuclear) antibodies. It provides requirements regarding the diagnostic tests used, instructions for laboratory procedure and evaluation, and recommendations for interpretation. For an optimal laboratory diagnostic process, it is useful to have an informative, tentative clinical diagnosis and an experienced laboratory diagnostician. In addition, the following key elements are recommended: initial screening using indirect immunofluorescence on carefully chosen HEp-2 cells beginning with a serum dilution of 1:80 and evaluation under a microscope with powerful illumination; results from a titer of 1:160 upwards being considered positive; internal laboratory quality control; and standardized interpretation. The aim is to improve diagnostic tests and care of patients with autoimmune diseases as a central concern of the European Autoimmunity Standardization Initiative (EASI). [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a disease of epidermal adhesion. Its pathogenesis is currently traced back to the action of autoantibodies against antigens located within the intercellular substance of keratinocytes, such as desmogleins and acetylcholine receptors. In the present paper, we sought to elucidate the non-IgG-mediated effects of PV sera on keratinocytes. Results showed that PV sera depleted of IgG were able to induce well-defined changes on keratinocyte morphology and metabolic activity. Indeed, PV IgG-free sera determined marked alterations on cell shape, accompanied by partial loss of keratinocyte–keratinocyte interactions within 48 h after treatment. Furthermore, PV IgG-depleted sera caused a sharp reduction of cell viability along with a less sustained weakening of intercellular adhesion strength. In light of the above findings, loss of cell–cell adhesion in PV occurs as a result of the cooperating action of both IgG and non-IgG-mediated mechanisms. These data have remarkable consequences on experimental models of PV and might open new “biological” approaches to its therapy. Thus, researchers are well advised that PV pathophysiology cannot be faithfully reproduced by leaving non-IgG serum factors out of consideration. J. Cell. Physiol. 212:563–567, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Is molecular mimicry the culprit in the autoimmune haemolytic anaemia affecting patients with COVID-19? Keywords: ankirin 1; autoantibodies; autoimmunity; COVID-19; molecular mimicry; severe acute respiratory syndrome coronavirus 2 EN ankirin 1 autoantibodies autoimmunity COVID-19 molecular mimicry severe acute respiratory syndrome coronavirus 2 e92 e93 2 07/20/20 20200715 NES 200715 The I British Journal of Haematology i recently published two papers describing autoimmune haemolytic anaemia (AIHA) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.1,2 AIHA is characterised by the destruction of red cells by autoantibodies, but the mechanism underpinning autoimmunity in patients with coronavirus disease 2019 (COVID-19) has yet to be elucidated. Ankirin 1, autoantibodies, autoimmunity, COVID-19, molecular mimicry, severe acute respiratory syndrome coronavirus 2. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

The heart can be seriously affected in human trichinellosis, and cardiac involvement can cause death. Experimental infections in rats have suggested the possible participation of immunopathological processes. The aim of the present paper was to investigate the possible presence in trichinellosis patient sera of antibodies recognizing host tissues and particularly the myocardium. Nineteen sera from late period trichinellosis patients, who acquired infection in the Poznan region (Poland), were tested by immunoblot on extracts from normal rat or human heart ventricle wall, spleen, placenta, kidney and skeletal muscle. Patients' sera recognized several antigens that were not recognized by normal sera. On rat and human heart ventricle wall, a high proportion of sera (42%) reacted with a protein of 68 kDa (P< 0.05 compared to normal sera). The reactivity with this antigen, however, was not significantly different in patients with or without cardiac involvement. When sera were tested on skeletal muscle we found that 47% reacted with a protein of 27 kDa and 53% reacted with a protein of 41 kDa (P<0.05 for both proteins, compared with normal sera). The reactivity against the 68 kDa antigen and against the 27 and 41 kDa skeletal muscle antigens was not observed on kidney, placenta and spleen extracts. Moreover, very few bands were observed on these tissues as compared to heart and skeletal muscle tissues, thus suggesting a high tissue specificity of the reactivity of trichinellosis sera. In conclusion, this study identifies organ-specific autoantibodies in trichinellosis patient sera, their role in the pathogenesis of cardiac involvement being still unclear. [ABSTRACT FROM AUTHOR]

For the majority of cases of acute liver failure in western Europe and North America an etiology cannot be defined. The condition is most often called fulminant non-A, non-B (NANB) hepatitis. Features such as female preponderance and presence of serum autoantibodies suggest a possible autoimmune basis. The aim of the present paper was to examine a possible human leukocyte antigen (HLA) association with fulminant NANB hepatitis.HLA A, B, and DR data of 55 adult Caucasian fulminant NANB patients were compared with those of 1449 local Caucasian controls.In Caucasian patients, homozygosity (but not heterozygosity) for the alleles A1, B8, and DR3 were associated with fulminant NANB hepatitis (Pcorrected = 0.02,<0.00001 and 0.002, respectively). Greatest relative risk (RR) was associated with homozygosity for the A1-B8-DR3 haplotype (P < 0.00001; RR: 12.8; 95% confidence interval[CI]: 5.7–22.3). HLA DR8 was also associated with development of the syndrome (RR: 4.2; 95%CI: 1.6–9.2).Homozygosity for the HLA haplotype A1-B8-DR3 confers susceptibility to the development of fulminant NANB hepatitis. This observation may imply a role for the immune response genes (which are flanked by HLA B and DR) in the pathogenesis of this syndrome. [ABSTRACT FROM AUTHOR]

Torres-Collado AX, Czaja AJ, Gelpí C. Anti-tRNP(ser)sec/SLA/LP autoantibodies. Comparative study using in-house ELISA with a recombinant 48.8 kDa protein, immunoblot, and analysis of immunoprecipitated RNAs.Liver International 2005: 25: 410–419.© Blackwell Munksgaard 2005Antibodies 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.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.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.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. [ABSTRACT FROM AUTHOR]

Highlights the papers presented during the 14th Congress of the European Academy of Allergology and Clinical Immunology in Berlin, Germany. Diagnosis and therapy of cellular immunodeficiencies; Immunodeficiencies due to humoral defects; Multifactorial pathogenesis of autoimmune diseases; Methods of demonstrating the presence of autoantibodies; Migratory responses of eosinophils and neutrophils from asthmatics.

This paper describes some of the characteristics of a suppressor cell which is capable of regulating a rat RBC-induced autoantibody response against mouse RBCs. This cell, which appears to function as an inducer of suppression on transfer to naive recipients, is sensitive to Iow doses of cyclophosphamide, and its generation is affected by iow doses of irradiation. However, the recipients of these cells arc insensitive to cyclophosphamide treatment, suppression still being induced in such animals. [ABSTRACT FROM AUTHOR]

HLA-G non classical class I locus shows a comparatively low polymorphism. It encodes for tolerogenic HLA molecules that may be important in autoimmunity and transplant (and foetal) rejection control. HLA-G molecules give negative signals to Natural Killer and T lymphocytes. In the present paper, a new allele, HLA-G*08, is described, which may be useful for monitoring transplants and for HLA and disease studies. [ABSTRACT FROM AUTHOR]

Angioedema has different causes and different clinical presentations that has two forms: acquired angioedema (types I and II) and hereditary angioedema. However, acquired angioedema type-II is a very rare disorder and there is no significant treatment. So, in this paper, we propose to report the successful use of combination therapy of deflazacort and danazol for two such cases. [ABSTRACT FROM AUTHOR]

Discusses the abstract of the research paper 'Autoantibodies to Immature Erythrocytes in Patients with the Anti-Phospholipid Antibody Syndrome,' by G. Davidyuk, et al, to be presented at the American Association of Blood Banks' 55th Annual Meeting on October 26-29, 2002.

The article presents a list of key words related to immunology used in the papers published in the August 1987 issue of the periodical "Immunology." Some of the key words are autoantibodies, autoantibody secretion, autoimmune phenomena, B-cell activation, benign monoclonal gammopathy, B lymphocytes, B-lymphoma cells namalwa, bovine alloreactive cytotoxic cells, C1 inhibitor, C3-IgG complexes, cap formation, delayed hypersensitivity, dendritic cells, dendritic cells and macrophages, dengue virus-induced cytotoxic factors, desensitization, endothelial cells, enteropathy, immunological, fibronectin and foot-and-mouth disease virus.

Discusses the abstract of the research paper 'The Use of DNA-Typing for Detection of an Alloantibody Anti-D Underlying Warm Autoantibody in a RhD[sup Va] Multiply Transfused Patient,' by J. Rosenblit, et al, to be presented at the American Association of Blood Banks' 55th Annual Meeting on October 26-29, 2002.

Discusses the abstract of the research paper 'Successful Transfusion of Kp(a-b+) Red Cells Incompatible for Anti-Kp[sup b]Autoantibody,' by M.A. Villa, et al, to be presented at the American Association of Blood Banks' 55th Annual Meeting on October 26-29, 2002.