The dissertation deals with studying the role of immunological, molecular and genetic factors in patients with systemic sclerosis (SSc) depending on the clinical forms and various types of lung injuries. Traditional clinical and instrumental methods with profound immunological screening (phagocytic activity of blood cells, lymphocyte phenotyping, cytokine balance and endothelium-dependent parameters), flow cytometry method, enzyme immunoassay and molecular genetic testing (expression miRNA29b) using polymerase chain reaction have been used in the research for the diagnostic of SSc. Patients with SSc and lung injuries had high activity of spontaneous neutrophil phagocytic index and physiological oxidative "stress" of these cells based on the reduced phagocytic activity of monocytes. Phenotyping of lymphocytes and their activation markers in patients with SSc and lung injuries characterized by decreased number of CD3 + lymphocytes with simultaneous increase in the number of activating forms CD3 +/CD HLA-DR+ and CD4+CD25+FoxP3+ cells , especially in the limited form of SSc with pulmonary hypertension. Cytokine balance characterized by increased levels of MCP- 1, especially in the patients with diffuse form of SSc, IL17-regardless of the clinical forms and amount of lymphocytes that produce IL17 directly in patients with SSc with lung injuries. Decreased level of IL12 and increased TGF-beta have been detected in patients with SSc and pulmonary fibrosis. High level of autoantibodies to RNA polymerase III was observed regardless of the clinical form in patients with SSc and lung injuries, increased autoantibodies to Scl70 was in patients with diffuse form of SSc pulmonary fibrosis and high level of endothelin-1 in patients with pulmonary hypertension and SSc, in addition further increased levels of anticentromere antibodies and circulating immune complexes was observed in these patients. The level of miRNA 29b expression was low in patients with SSc and pulmonary fibrosis in comparison with patients with SSc without lung injuries and healthy individuals. Logistic regressive analysis of clinical, immunological, molecular and genetic parameters helped to identify the following diagnostic criteria of lung injuries in patients with SSc: duration of illness, the value of spontaneous phagocytic index of neutrophils in the blood, levels of IL17 in blood serum, and miRNA 29b expression on blood cells; pulmonary fibrosis - the age of the patient , the value of the spontaneous index of monocytes in the blood, levels of MCP-1 , IFN-gama, TGF-beta in blood serum and miRNA29b expression on blood cells, pulmonary hypertension - meaning of spontaneous phagocytic index of neutrophils in the blood, the number of CD3+/CDHLA-DR+, CD4+CD25+Fox P3+- lymphocyte, levels of endothelin-1, IL17 in blood serum. Clinical, immunological, molecular and genetic risk factors for development of lung injuries patients with SSc.
