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      Anti-Idiotypic Agonistic Antibodies: Candidates for the Role of Universal Remedy

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          Abstract

          Anti-idiotypic antibodies (anti-IDs) were discovered at the very beginning of the 20th century and have attracted attention of researchers for many years. Nowadays, there are five known types of anti-IDs: α, β, γ, ε, and δ. Due to the ability of internal-image anti-IDs to compete with an antigen for binding to antibody and to alter the biologic activity of an antigen, anti-IDs have become a target in the search for new treatments of autoimmune illnesses, cancer, and some other diseases. In this review, we summarize the data about anti-IDs that mimic the structural and functional properties of some bioregulators (autacoids, neurotransmitters, hormones, xenobiotics, and drugs) and evaluate their possible medical applications. The immune system is potentially able to reproduce or at least alter the effects of any biologically active endogenous or exogenous immunogenic agent via the anti-idiotypic principle, and probably regulates a broad spectrum of cell functions in the body, being a kind of universal remedy or immunacea, by analogy to the legendary ancient goddess of universal healing Panacea (Πανάκεια, Panakeia in Greek) in the treatment and prevention of diseases, possibly including non-infectious somatic and even hereditary ones.

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          Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome.

          Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors. Autoantibodies against G-protein coupled receptors were shown to play a pathogenic role in several autoimmune diseases. Here, serum samples from a patient cohort from Berlin (n=268) and from Bergen with pre- and post-treatment samples from 25 patients treated within the KTS-2 rituximab trial were analysed for IgG against human α and β adrenergic, muscarinic (M) 1-5 acetylcholine, dopamine, serotonin, angiotensin, and endothelin receptors by ELISA and compared to a healthy control cohort (n=108). Antibodies against β2, M3 and M4 receptors were significantly elevated in CFS patients compared to controls. In contrast, levels of antibodies against α adrenergic, dopamine, serotonin, angiotensin, and endothelin receptors were not different between patients and controls. A high correlation was found between levels of autoantibodies and elevated IgG1-3 subclasses, but not with IgG4. Further patients with high β2 antibodies had significantly more frequently activated HLA-DR+ T cells and more frequently thyreoperoxidase and anti-nuclear antibodies. In patients receiving rituximab maintenance treatment achieving prolonged B-cell depletion, elevated β2 and M4 receptor autoantibodies significantly declined in clinical responder, but not in non-responder. We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and β adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy. The association of autoantibodies with immune markers suggests that they activate B and T cells expressing β adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.
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            Towards a network theory of the immune system.

            N K Jerne (1973)
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              GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis

              Autoantibodies have been associated with autoimmune diseases. However, studies have identified autoantibodies in healthy donors (HD) who do not develop autoimmune disorders. Here we provide evidence of a network of immunoglobulin G (IgG) autoantibodies targeting G protein-coupled receptors (GPCR) in HD compared to patients with systemic sclerosis, Alzheimer’s disease, and ovarian cancer. Sex, age and pathological conditions affect autoantibody correlation and hierarchical clustering signatures, yet many of the correlations are shared across all groups, indicating alterations to homeostasis. Furthermore, we identify relationships between autoantibodies targeting structurally and functionally related molecules, such as vascular, neuronal or chemokine receptors. Finally, autoantibodies targeting the endothelin receptor type A (EDNRA) exhibit chemotactic activity, as demonstrated by neutrophil migration toward HD-IgG in an EDNRA-dependent manner and in the direction of IgG from EDNRA-immunized mice. Our data characterizing the in vivo signatures of anti-GPCR autoantibodies thus suggest that they are a physiological part of the immune system.
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                Author and article information

                Journal
                Antibodies (Basel)
                Antibodies (Basel)
                antibodies
                Antibodies
                MDPI
                2073-4468
                28 May 2020
                June 2020
                : 9
                : 2
                : 19
                Affiliations
                [1 ]Department of Pathology and Laboratory of the Mosaic of Autoimmunity, Saint Petersburg State University, 199034 Saint Petersburg, Russia; aliya.stanova@ 123456mail.ru (A.K.S.); varvara-ryabkova@ 123456yandex.ru (V.A.R.); utekhin44@ 123456mail.ru (V.J.U.); shoenfel@ 123456post.tau.ac.il (Y.S.)
                [2 ]Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; tillib@ 123456genebiology.ru
                [3 ]Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
                [4 ]Saint Petersburg Research Institute of Phthisiopulmonology, 191036 Saint Petersburg, Russia
                [5 ]Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, affiliated to Tel Aviv University School of Medicine, Tel-Hashomer, Ramat Gan 52621, Israel
                Author notes
                [* ]Correspondence: elpach@ 123456mail.ru
                Author information
                https://orcid.org/0000-0001-6973-9901
                https://orcid.org/0000-0001-6359-0026
                Article
                antibodies-09-00019
                10.3390/antib9020019
                7345059
                32481667
                7dbc8e97-5104-489e-aab0-b39caab35157
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 April 2020
                : 26 May 2020
                Categories
                Review

                anti-idiotypic antibodies,agonistic autoantibodies,autacoid,drug,hormone,neurotransmitter

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