[IGG4-related diseases in endocrinology].

Immunoglobulin-G4-related disease (IgG4-RD) is a chronic immunomediated pathology of different organs of local or systemic nature, which has been established as a separate clinical entity in the early 2000s and is characterized by storiform fibroid inflammation of the affected tissues, their increase, and elevated serum immunoglobulin-G4 (IgG4) levels. The most common manifestations of the disease are major salivary and lacrimal gland enlargement, lymphadenopathy and type 1 autoimmune pancreatitis (AIP1), however, other organs may be also involved (the thyroid, eyes, meninges, heart, lungs, kidneys, aorta, upper airways, mesentery, etc.). The effectiveness of treatment of IgG4-RD, as well as other pathological conditions, is also determined by the timely diagnosis. However, the latter is complicated due to the variety of clinical manifestations and rather variable diagnostic criteria. It is necessary to constantly update the evidence-based knowledge and diagnostic algorithms within this pathology in order to overcome the difficulties, and involve immunologists, endocrinologists, pathologists and specialists in other spheres. This review provides information about the etiology, pathogenesis, and current methods of diagnosis and treatment of IgG4-related diseases, as well as examples of some manifestations of IgG4-RD that an endocrinologist may face in practice.

Erythropoietin Directly Affects Human Macrophage Functionality.

OBJECTIVE: We studied direct effects of Erythropoietin (Epo) on functional properties of human monocytes/macrophages (Mc/Mphs) in vitro. METHODS: Cells expressing CD14 marker were isolated from human peripheral blood mononuclear cells (PBMCs) by positive magnetic separation. Mc/Mphs were cultured without or with bacterial lipopolysaccharide (LPS) in the absence or presence of Epo for 24 h. RESULTS: We showed that Epo treatment hoticeably reduces the percentages of CD14+ cells, CD124 (alpha subunit of IL-4 receptor)+ cells and CD197 (CCR7)+ cells in non-activated Mph cultures without affecting the levels of CD16 (low-affinity Fc-receptor)+ and CD119 (interferon-γ (IFN-γ) receptor)+ cells. Epo also markedly reduced percentages of CD197+ cells in LPS-activated Mc/Mphs, without significantly affecting the expression of all other molecular markers studied. In addition, Epo caused moderate up-regulation of interleukin-1ß (IL-1ß) and IL-6 production in resting Mc/Mph cultures, as compared to the down-regulation of IL-1ß and IL-6 production in LPS-activated cells. No Epomediated effects on tumor necrosis factor-α (TNF-α) and IL-10 production were observed. CONCLUSION: Our data suggests that Epo effects on Mph functionality are largely dependent on the baseline activation status of these cells, and that Epo exerts no distinct direct effects on the particular Mph polarization pathway.

Direct effects of interleukin-7 on the function of human T cells in vitro.

СD3+ T lymphocytes were isolated by positive magnetic separation from the peripheral blood of healthy donors. In the absence of any additional activating stimuli, interleukin-7 (IL-7) was shown to augment the levels of T cells expressing CD25 activation marker both in СD4-positive and in CD4-negative effector memory (CD45RA-CD197-) T cell subsets, as well as in terminally differentiated (CD45RA+CD197-) Т cells, without significantly affecting the activation status of naive (CD45RA+CD197+) and central memory (CD45RA-CD197+) T cells. In addition, IL-7 noticeably enhanced the production of IL-2, interferon-γ (IFN-γ), and IL-10, but not IL-4, in T cells. The direct effects of IL-7 on T cell activation induced in vitro by MACSiBead™ particles coated with CD2, CD3, and CD28 antibodies (Abs) were also investigated. Upon cell activation, IL-7 significantly augmented the levels of CD25+ T cells in naive (CD45RA+CD197+), central memory (CD45RA-CD197+), and effector memory (CD45RA-CD197-) T-cell compartments. In addition, IL-7 facilitated activation of СD4- (but not CD4+) terminally differentiated effector (CD45RA+CD197-) Т cells. Finally, IL-7 was found to upregulate the production of IL-2, IFN-γ, IL-4, and IL-10 by activated T cells. In conclusion, we speculate that IL-7 is capable of enhancing functional T cell activity without causing significant functional inbalance between various T cell subsets.