Status of cytokines and their receptors in the genesis of autoimmune endocrinopathy

Saprina T.V., PhD, Prokhorenko T.S., Zima A.P., MD, professor Ryazantseva N.V., MD, аcademician of RAMS Novitsky V.V., MD

Siberian State Medical University, Tomsk, Russia

Status of cytokines and their receptors in the genesis of autoimmune endocrinopathy

Introduction

The problem of diseases associated with autoimmune disorders, is becoming increasingly important due to the increased morbidity, the difficulty of predicting the nature of the disease and the lack of clear technologies for prevention of complications. It is known that the features of the formation and course of autoimmune endocrinopathies determined by the immune system [1, 2]. In particular, the nature of the immune system depends on the clinical course and outcome of autoimmune diabetes and autoimmune thyropathy (autoimmune thyroiditis -AIT, Graves' disease - GD) [3, 4, 8].

Purpose

To assess the cytokines (IL-2, IL-4, TNFα) production level and their receptors expression in autoimmune endocrine diseases (diabetes mellitus type 1 (DM1), latent autoimmune diabetes of adults (LADA), autoimmune thyroiditis (AIT), Graves' disease (GD)).

Materials and Methods

We examined 138 patients with type 1 diabetes mellitus and LADA, 73 patients with AIT and GD, 50 healthy human volunteers. The content of CD3, CD4, CD8, CD16/56low and CD19-cells, the number of lymphocytes, membrane-bound receptors expression (IL2R, IL4R, TNF-RI) was assessed by flow cytometry («Becton Dickinson», USA), the contents of IL2, IL4, TNFα, sTNF-RI in the culture medium of blood mononuclear leukocytes ("Vector-Best", Russia, «BenderMedSystems», Austria) - by ELISA. To assess the reliability of differences in the groups we used the Mann-Whitney test (for independent samples).

The results

Initiation and implementation of the effects of autoimmune inflammation involve a violation of the ratio Th-lymphocyte clone and the action of regulatory cytokines secreted by immune cells [5, 6]. We assessed the production level of IL-2, IL-4, TNFα and their receptors in autoimmune endocrine diseases, affecting pancreas and thyroid gland. It is established that the AIT and autoimmune diabetes (T1D) associated with the rapid loss of insulin secretion, caused by activation of the cellular type of immune response. This is reflected in cytokine production profile of Th1-(IL-2, TNFα) and Th2- leukocytes (IL-4). It was shown decreasing of soluble form of the TNFα receptor production (sTNF-R) and increasing of the TNF-RI and IL4-R lymphocytes expressing number in patient with DM 1. In patient with AIT was demonstrated the increasing of the TNF-RI and IL4-R expressing lymphocytes, parallel with the increase of CD25+-lymphocytes (IL2-R).

In LADA group was shown an increasing of TNFα, IL-4 production and their receptor expression, reducing concentration of sTNF-RI, which indicates the involvement in the pathogenesis of disease equal Th1-, Th2-and clones of lymphocytes. In addition, marked reduction of the number of B-lymphocytes was observed in LADA. It is important to note that the severity of the changes TNFα reception in LADA is less pronounced than in type 1 diabetes, reflecting differences in the mechanisms of these variants of autoimmune diabetes.

In contrast to the AIT, GD group was characterized by the activation of humoral immunity, reduced TNFα production by mononuclear leukocytes. These data well consistent with the ideas about the basic mechanisms of GD - the synthesis thyroid-stimulating hormone receptor antibodies by activated B-cell, followed by thyroid hormones overproduction [7]. A common feature of autoimmune thyroid diseases (AIT and BG) was reducing the number of circulating NK-cells (CD16+ / 56^low).

Conclusion

These data justify further study of molecular and cellular mechanisms of formation and the clinical manifestations of autoimmune endocrine diseases. It also leads to the development of new approaches to forecasting the outcome of autoimmune disease, as well as a personalized correction technology of cytokine - mediated immune cells disregulation, this implies a wider therapeutic window for preventive strategies including immune-based therapies.

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