Wide Range Of Autoantibodies Research Articles

Autoimmune Movement Disorders Complicating Treatment with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) may trigger autoimmune neurological conditions, including movement disorders (MD). The aim of this study was to characterize MDs occurring as immune-related adverse events (irAEs) of ICIs. A systematic literature review of case reports/series of MDs as irAEs of ICIs was performed. Of 5682 eligible papers, 26 articles with 28 patients were included. MDs occur as a rare complication of cancer immunotherapy with heterogeneous clinical presentations and in most cases in association with other irAEs. Inflammatory basal ganglia T2/fluid attenuated inversion recovery abnormalities are rarely observed, but brain imaging is frequently unrevealing. Cerebrospinal fluid findings are frequently suggestive of inflammation. Half of cases are associated with a wide range of autoantibodies. Steroids and ICI withdrawal usually lead to improvement, even though some patients experienced relapses or a severe clinical course. MDs are a rare complication of ICIs that should be promptly recognized to offer patients a correct diagnosis and treatment.

Anti-dsDNA antibodies in the classification criteria of systemic lupus erythematosus

Anti-double stranded DNA (dsDNA) antibodies play an important role in the diagnosis, classification and management of systemic lupus erythematosus (SLE), an autoimmune disease characterized by heterogeneous clinical manifestations and a wide range of autoantibodies, which makes the diagnosis quite challenging. In the absence of diagnostic criteria, classification criteria have been used for many decades. The first classification criteria for SLE were formulated in 1971 by the American College of Rheumatology (ACR), followed by two revisions in 1982 and 1997. In order to improve their clinical performance and to reflect new knowledge on autoantibodies, new classification criteria for SLE were issued in 2012 by the Systemic Lupus International Collaborating Clinics (SLICC). These criteria proposed to classify only patients that have at least one immunologic criterion, overcoming SLE classification based solely on clinical manifestations. In 2019, the European League Against Rheumatism (EULAR)/ACR proposed new criteria that aimed to maintain the high specificity of the ACR criteria with a sensitivity close to the SLICC 2012 criteria. These 2019 criteria reinforced the importance of autoantibodies in SLE diagnosis, assigning the highest score (6 points) to anti-dsDNA antibodies in the fully weighted scoring of the disease. The current criteria require the use of an anti-dsDNA assay with at least 90% specificity, such as the Crithidia luciliae immunofluorescence test (CLIFT) or FARR assay. However, the criteria do not comment on all the tests currently widely used in clinical laboratories. Neither do they consider the technological evolutions, nor standardization issues. Since strict adherence to any of the classification criteria, including the serological items, could lead to possible misclassification of SLE and/or delayed diagnosis, test characteristics of the distinct immunoassays should be taken into consideration.

Study of Peptidyl Arginine Deiminases 4 (PAD 4) Antibodies in Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is one of the most commonly occurring form of inflammatory polyarthritis. If untreated,20%–30% of RA patients become debilitated within the first three years following initial diagnosis. The clinical examinationoften fail to identify patients with early RA partly due to heterogeneity of disease presentation and course. To meet the needfor improved diagnostic and prognostic tests, various serum biomarkers are being assessed, including a wide range ofautoantibodies. Autoantibodies against peptidyl arginine deiminase type 4 (PAD-4) have recently been described as a specificbiomarker in subjects with clinically apparent RA. In this study, we tested the presence of anti-PAD4 antibodies in 40Egyptian subjects with RA and their first degree relatives in order to determine whether these autoantibodies play a role inearly disease evolution. In addition, we aimed to describe the Anti-PAD4 relation to anti-CCP autoantibodies, and potentialassociations with a more severe RA phenotype. The study was carried out on total of 100 subjects divided into; 40 RApatients, 40 of first degree relatives (sister or brother) of RA patients and 20 matched controls. Results: The resultsindicated that the serum level of Anti-PAD 4 is increased in Egyptian RA patients and their relatives and has a positiveassociation with disease activity. Also its level together with Anti-CCP provides a good diagnostic tool of RA. Conclusion:The serum level of Anti-PAD4 may provide diagnostic information of RA and may be considered as an early marker of thedisease among the first degree relatives of RA patients. [Egypt J Rheumatology & Clinical Immunology, 2016; 4(1): 59-66]

Diagnostic Utility of Auto Antibodies in Inflammatory Nerve Disorders

A wide range of autoantibodies have been described in immune-mediated nerve disorders that target glycans borne by glycolipids and glycoproteins enriched in the peripheral nerves. Their use as diagnostic biomarkers is very widespread, despite some limitations on sensitivity and specificity, and the lack of standardized assays and access to quality assurance schemes. Although many methods have been applied to measurement, ELISA, in the form of commercial kits or in-house assays, still remains the most widely available and convenient assay methodology.Some antibodies have a particularly robust and widely appreciated clinical significance. Thus, the anti-MAG IgM antibodies that are found in IgM paraprotein related neuropathies define a relatively uniform clinical and prognostic phenotype. IgG antibodies against gangliosides GM1 and GD1a are strongly associated with motor axonal variants of Guillain-Barré syndrome, and anti-GQ1b with Miller Fisher syndrome. In other chronic neuropathies, antibodies against disialylated gangliosides including GD1b and GD3 are detected in ataxic neuropathies, usually associated with an IgM paraprotein, and antibodies against GM1 and the complex GM1:GalC are frequently found in multifocal motor neuropathy. Unfortunately, autoantibodies strongly associated with the diagnosis of chronic inflammatory demyelinating polyneuropathies and with demyelinating forms of GBS are still lacking.Identification of autoantibodies that map onto a specific clinical phenotype not only allows for improved classification, but also provides better understanding of the pathophysiology of inflammatory neuropathies and the potential for therapeutic interventions.

Anti‐interleukin‐5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin‐5 levels

Atherosclerotic diseases, such as coronary artery disease and peripheral artery disease, are systemic disorders and among the leading causes of mortality and morbidity throughout the world. However, the exact pathophysiological mechanisms underlying the development of atherosclerosis remain unknown; currently, atherosclerosis is thought to involve an inflammatory process. Systemic inflammatory reactions and accumulation of immune cells in atherosclerotic lesions in situ are considered essential. We have comprehensively analyzed autoantibodies in patients with atherosclerosis by means of a newly developed high-throughput autoantibody analysis system. A wide range of autoantibodies was found in sera from patients with atherosclerosis. After we statistically analyzed the titers of each autoantibody with conventional techniques, the results underwent text-mining analyses based on natural language processing. Combinatory analysis revealed a close association between anti-interleukin (IL)-5 antibody and atherosclerosis. Titers of anti-IL-5 antibodies and serum IL-5 concentrations were also closely associated with other risk factors, such as low-density lipoprotein cholesterol, serum creatinine, fasting plasma glucose, gender, and age, suggesting that suppressed IL-5 function mediated by autoantibodies in patients with atherosclerosis plays an important role in the disease process. To validate the clinical significance of these findings, we computed the specificity and sensitivity of titers of anti-IL-5 autoantibodies for human atherosclerosis. When antibody titers of 1.49 were assumed to predict the presence of atherosclerosis, the sensitivity was 95.0% and the specificity 91.0%, with an area under the curve of 0.940. Our results provide important clues to understanding the role of autoantibody-mediated immune reactions in human atherosclerosis and suggest novel therapeutic opportunities for management of the disease.

Coexistence of thyroid autoimmunity with other autoimmune diseases: Friend or foe? Additional aspects on the mosaic of autoimmunity

Autoimmunity encompasses a wide spectrum of diseases from organ-specific diseases like Hashimoto thyroiditis, to systemic diseases such as systemic lupus erythematosus. These diseases are characterized by inflammation and the production of a wide range of autoantibodies directed against multiple autoantigens. Although their etiology is still poorly understood, genetic, immunological, hormonal, and environmental factors are major predisposing and triggering factors. These multiple factors, like pieces in a mosaic, may interplay in different forms, leading to the expression of various autoimmune manifestations and diseases. This phenomenon, which has been referred by us as the “mosaic of autoimmunity”, illuminates the diversity of autoimmune manifestations among susceptible individuals. From this theoretical framework we conducted a wide search of the literature, on the prevalence of thyroid autoimmunity, the commonest of the autoimmune conditions, among other autoimmune diseases, and discuss the possible clinical significance of this association.

IMMUNOLOGICAL ABNORMALITIES IN PATIENTS WHO HAD THE OCULOMUCOCUTANEOUS SYNDROME ASSOCIATED WITH PRACTOLOL THERAPY

Patients with and without adverse reactions on practolol therapy showed altered immune responses. There was cutaneous anergy to Candida albicans and streptokinase/streptodornase antigens and depression of lymphocyte function in vitro. Anticomplementary activity and a wide range of autoantibodies were found in patients who had received practolol.