Особливості перебігу пневмоній при грипі у осіб з поліморфізмом генів TLR-2, TLR-3, TLR-4

Abstract

Цель - проанализировать течение гриппа, осложненного пневмонией, у пациентов с полиморфизмом генов TLR-2 Arg753Gln, TLR-3 Leu412Phe, TLR-4 Asp299Gly. В исследование были включены 36 пациентов (25 женщин и 11 мужчин) преимущественно молодого и среднего возраста, не имеющие общепризнанных факторов риска развития тяжелого и осложненного течения гриппа. Было установлено что у преимущественного большинства (69,5%) больных гриппом, осложненным пневмонией,определялись мутации в генах TLR-2, TLR-3, TLR-4. Мутантные генотипы Asp/Gly TLR-4 и Arg/Gln TLR-2 выявлялись, как правило, в комбинации с полиморфизмом гена Leu412Phe TLR-3. Показано, что люди с мутантным гомозиготным генотипом TLR-3 и комбинацией мутантных генотипов TLR-2, TLR-3 TLR-4 составляют группу повышенного риска развития вирусной пневмонии у больных гриппом, а наличие мутантных генотипов Arg/Gln TLR-2, Leu/Phe, Phe/Phe TLR-3 и Asp/Gly TLR-4 является прогностически неблагоприятным признаком в отношении тяжести течения пневмонии, развития ПОН и ОРДС, а также летального исхода; Introduction. The most number of lethal cases due to grippe is connected with complications development with pneumonias majority. The search of markers determining the risk of severe and complicated forms of grippe development among alleles of TLR genes is a new promising area of research. The objective of research is to analyze grippe course complicated by pneumonia in patients with TLR-2 gene Arg753Gln, TLR-3 gene Leu412Phe, TLR-4 Asp299Gly polymorphism. Methods. There were 36 patients (25 females and 11 males) included into the research; they were mainly of young and middle age (40,21,72 in average) without established risk factors of severe and complicated grippe course. Pneumonia has resulted to death for 4 (11,1%) patients. The dead patients’ age was from 26 to 52 (42,53,09 in average). The results. The conducted researches have shown that there was a mutation of TLR-2, TLR-3, TLR-4 genes in the majority of patients (69,5%) with grippe complicated by pneumonia. There was a standard distribution of TLR genes alleles in one third of the patients while the mutations (the most common of TLR-3 (66,6%) genes) were diagnosed in rest of the patients. Viral pneumonia was diagnosed solely (100,0%) in patients with TLR genes polymorphism, primarily TLR-3 (83,3%). The severity of pneumonia course has depended on the presence of TLR-3 gene polymorphism. TLR-3 gene Leu412Phe polymorphism has been revealed more often in patients with severe course of pneumonia compared with moderate (83,3% against 50,0%). Conclusions. The conducted research has shown that patients with TLR-2, TLR-3, TLR-4 genes polymorphism have the increased risk of pneumonia development in case of grippe. The patients with TLR-3 mutant genotype and combination of TLR-2, TLR-3, TLR-4 mutant genotypes are in risk group for viral pneumonia development in case of grippe. The presence of Arg/Gln TLR-2, Leu/Phe, Phe/Phe TLR-3 and Asp/Gly TLR-4 mutant genotypes is the predictable unfavorable feature in relation to the severity of pneumonia course in case of grippe, the development of multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS) as well as fatal outcome.