The dynamics of immunological parameters in early stages after bilateral lung transplantation in patients with various pulmonary pathology

Abstract

Background. The diseases leading to the need for lung transplantation include chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1-antitrypsin deficiency, idiopathic pulmonary hypertension, histiocytosis X, and sarcoidosis. Primary lung transplant dysfunction is a frequent complication after transplantation and represents a multifactorial injury of the transplanted lung, its pathogenesis being associated with a severe hypoxemia of the lung transplant and diffused damage to the alveoli. The clinical presentation is in many ways similar to an acute respiratory distress syndrome, which pathogenesis is primarily effected by the activation of immune system cells. The cytokine production by immunocompetent cells, the synthesis of reactive oxygen and nitrous oxide, being the mediators of inflammation, trigger inflammatory processes in the lungs; the immunoglobulin synthesis derangements also lead to the development of inflammatory abnormalities in the lungs and a poor transplantation outcome.The objective was to study the immunological response in the lung transplant recipients suffering from the underlying disease of various etiology and to determine the immunological predictors of adverse outcome in the early period after bilateral lung transplantation.Material and methods. Twenty nine patients were examined within 2 weeks after lung transplantation: Group 1 comprised 10 patients with cystic fibrosis (6 women, 4 men) aged 27.8 ± 2.7 years; Group 2 included 19 patients (7 women, 12 men) at the age of 38.5 ± 10.4 years having other lung diseases. Mortality was 10% (1 patient) in Group 1, and 52.5% (10 patients) in Group 2. The patients were followed-up according to the standard protocol of postoperative treatment and immunosuppression therapy shemes. Immunological monitoring included the lymphocyte phenotyping, and the assessment of phagocytic activity of neutrophils, the HCT-test, the blood levels of immunoglobulins (Ig) A, M, G, circulating immune complexes, and C-reactive protein. Statistical significance was assessed at p <0.05.Results. On day 5, the T-lymphocyte count in patients of Group 1 was 674 cells/μL (Me), which was 26.7% lower than lower limit of the reference range, but 2.5 times higher than that in patients of Group 2 (266 cells/μL). The number of T-lymphocytes in patients of the 2nd group was recorded at 71.1% below the lower limit of the reference interval (p < 0.05). The blood level of IgA (Me) in patients of Group 1 was within the normal range (Ме– 1.9 g/L), the blood level of IgA (Me) in patients of Group 2 was 1.4 g/L, which was 26.3% lower than below the lower limit of the reference values and lower than in Group 1 (p < 0.05).By day 13, the count of T-lymphocytes in Group 1 had increased 2.2 times compared to day 5, reaching the reference values (Me), and made 1479 cells/μL. In the 2nd group, there was a 1.5-fold increase in T-lymphocyte count (Me 408 cells/μL), which was 3.7 times lower than the lower limit of the reference range and lower than in the 1st group (p < 0.05). The level of IgA in patients of the 1st group increased by 20.8% and amounted to 2.4 g/L (Me), and in patients of the 2nd group, the level of IgA for 2 weeks remained almost unchanged (Me 1.5 g/L ) and was 1.7 times lower than in the 1st group (p < 0.05).Conclusions. On day 5 after transplantation, the patients with cystic fibrosis demonstrated the increase in the T-lymphocyte count and IgA level by 2.5 and 1.4 times, respectively, compared to the patients with other lung diseases. By the end of week 2, T-lymphocyte and IgA values in patients with cystic fibrosis, unlike patients with other lung diseases, had reached the reference range. The T-lymphocyte count and the concentration of IgA below the reference range in the first 2 weeks after lung transplantation were the immunological predictors of adverse outcome.