Multiplex Autoantibody Detection in Patients with Autoimmune Polyglandular Syndromes.

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8-97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.

[Corrigendum: hypoglycemic syndrome in patients with monoclonal gammopathy [problems of endocrinology 2020;65(6) doi: 10.14341/probl12266]].

The article «Hypoglycemic syndrome in patients with monoclonal gammopathy» published by Solovyev MV, Yukina MY, Troshina EA in Problems of Endocrinology 2020;65(6) (doi: 10.14341/probl12266) contains wrong data in «Conflict of interests» section. Correct information is: «Manuscript preparation and publication was supported by the Russian Science Foundation (project No. 17-75-30035). The information given in the article about the sources of funding should not have any significant effect on the perception of information by readers and / or interpretation of the data presented. The authors regret the incorrect information in a previously published article.

[Hypoglycemic syndrome in patients with monoclonal gammopathy].

One of the reasons for the development of hypoglycemia is the synthesis of autoimmune antibodies to insulin or its receptor – insulin autoimmune syndrome (IAS). The largest number of cases of this syndrome is described in the Japanese population. The antibodies to insulin are most often polyclonal immunoglobulins. In monoclonal gammopathy of undetermined significance and multiple myeloma secreted pathological monoclonal immunoglobulin may have an affinity for human insulin, which induces the development of IAS. The prolonged persistence of episodes of hypoglycemia of unknown origin requires the exclusion of the monoclonal nature of secreted antibodies to insulin. Often the presence of pathological secretion for a long time is not recognized due to the absence of other manifestations of the disease. The manifestation of gammopathy is represented by a wide range of symptoms and syndromes requiring the collaboration of doctors of various specialties. This review summarizes the literature on IAS in patients with monoclonal gammopathy, whose disease debuted from episodes of spontaneous hypoglycemia. When hemoblastosis remission is achieved (when the secretion of the pathological protein is minimal or not determined), the glucose, insulin, and antibodies levels of insulin normalize, and when multiple myeloma recurs, episodes of hypoglycemia resume. The onset of the disease from the IAS can be considered as a new criterion for symptomatic multiple myeloma, dictating the need for the initiation of specific therapy.

[The role of HLA genes: from autoimmune diseases to COVID-19].

Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II - to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm¼ in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.