INFLUENCE OF HLA-DRB1* ALLELIC SETS ON THE DEVELOPMENT OF TUBERCULOSIS IN CHILDREN

According to the WHO data, tuberculosis still represents a serious public health problem worldwide. Deterioration of socio-economic conditions in the population complicates epidemic situation for tuberculosis inRussia, thus leading to increase in acute progressive and complicated forms of tuberculosis in children and, consequently, to worsening structure of its clinical forms. Objectives: to determine associations between certain HLA-DRB1 alleles and risk of tuberculosis development in children. We examined 188 children aged from 3 to 14 years with various manifestations of tuberculous infection. Along with thorough examination of the patients, including multi-spiral CT scans of chest, we undertook genotyping of HLA-DRB1 alleles. Activity of tuberculous infection was determined by a set of immunological tests, i.e., tuberculin skin test, DIASKINTEST® (recombinant allergen of tuberculosis DIASKINTEST®). X ray diagnostics was performed with multi-spiral «Aquilion-32» computed tomograph (Toshiba), according to standard procedures. Molecular genetic typing of HLA-DRB1 alleles was performed by polymerase chain reaction (PCR-SSP), using standard commercial kits PROTRANS Ceclerplate System Protrans HLA-DRB1*. The children were divided into two groups: I group, 90 healthy children, II group, 98 children with tuberculosis. A comparisons group consisted of healthy donors (n = 346). Statistical processing of genetic material included evauation and analysis of the following parameters: frequency distribution of the antigen (F), χ2 criterion for significance (chi-square), the relative risk ratio (RR), etiologic fraction (EF), preventive fraction (PF). Children of the II group had significantly higher *04 allele HLADRB1*, as compared with control group (36.7% vs. 21.1%, χ2 = 10.08; р < 0.01). This finding may suppose a predisposal of these allele carriers to development of tuberculosis. At the same time, the rates of *07 (14.3% vs. 27.5%, χ2 = 7.15, р < 0.01) and *15 (18.4% vs. 28.3%, χ2 = 3.92; р < 0.01) HLA-DRB1* alleles were significantly lower, thus suggesting a protective effect of this allele. *04 allele seems to be a predisposing factor, whereas *07 and *15 alleles are protective for development of tuberculosis in children. 

1. Аксенова В.А., Севостьянова Т.А., Клевно Н.И. Туберкулез у детей и подростков в России к началу XXI в. // Вестник Росздравнадзора, 2013. № 3. С. 19-23. [Aksyonova V.A., Sevostyanova T.A., Klevno N.I. Tuberculosis in children and adolescents in Russia at the beginning of the XXI century. Vestnik Roszdravnadzora = Bulletin of Roszdravnadzor, 2013, no. 3, рр. 19-23. (In Russ.)]

2. Аксенова В.А., Барышникова Л.А., Севостьянова Т.А., Клевно Н.И. Туберкулез у детей в России и задачи фтизиатрической службы и общей педиатрической службы по профилактике и раннему выявлению заболевания // Туберкулез и болезни легких, 2014. Т. 91, № 3. С. 40-46. [Aksyonova V.A., Baryshnikova L.A., Sevostyanova T.A., Klevno N.I. Tuberculosis in children in Russia and the problem of TB service and general pediatric services for prevention and early detection of the disease. Tuberkulez i bolezni legkikh = Tuberculosis and Lung Disease, 2014, Vol. 91, no. 3, pp. 40-46. (In Russ.)]

3. Арчакова Л.И., Кноринг Б.Е., Павлова М.В., Смирнов М.Н. Иммуногенетический профиль больных туберкулезом легких и возможности совершенствования терапии // Вестник Санкт-Петербургского университета. Серия 11: Медицина. 2009. № 2. С. 61-66. [Archakova L.I., Knoring В.Е., Pavlova М.V., Smirnov M.N. Immunogenetic profile of patients with pulmonary tuberculosis and possibilities of its therapy perfection. Vestnik SanktPeterburgskogo universiteta. Seriya 11 = Bulletin of St. Petersburg State University, 2009, no. 3, рр. 61-66. (In Russ.)]

4. Хаитов Р.М., Алексеев Л.П., Болдырева М.Н., Сароянц Л.В. Полиморфизм генов иммунного ответа и его роль в противоинфекционной защите // Иммунология, 2013. Т. 34, № 3. С. 132-144. [Khaitov P.M, Alexeev L.P., Boldyreva M.N., Saroyants L.V. Polymorphism of immune response genes and its protective role against infections. Immunologiya = Immunology, 2013, Vol. 34, no. 3, pp. 132-144. (In Russ.)] 5. Левашев Ю.Н., Шеремет А.В., Гришко А.Н. Динамика развития эпидемической ситуации с туберкулезом на территориях северо-западного федерального округа РФ в 2001-2006 гг. // Проблемы туберкулеза и болезней легких, 2008. Т.85, № 12. С. 3-

5. [Levashev Y.N., Sheremet A.V., Grishko A.N. The dynamics of the epidemic situation of tuberculosis in the North-West Federal District of Russia in 2001-2006. Problemy tuberkuleza i bolezney legkikh = Problems of Tuberculosis and Lung Disease, 2008, Vol. 85, no. 12, pp. 3-5. (In Russ.)]

6. Овсянкина Е.С., Серебрякова Т.В., Губкина М.Ф., Авербах М.М. Туберкулинодиагностика у детей с отягощенным аллергическим анамнезом // Проблемы туберкулеза и болезней легких, 2008. № 5. С. 25-29. [Ovsyankina E.S., Serebriakova T.V., Gubkinа M.F., Auerbach M.M. Tuberculin in children with a history of allergic history. Problemy tuberkuleza i bolezney liogkikh = Problems of Tuberculosis and Lung Disease, 2008, no. 5, pp. 25-29. (In Russ.)]

7. Дорошенкова А.Е., Ставицкая Н.В. Генетические особенности детей, больных различными формами туберкулеза органов дыхания // Туберкулез и болезни легких, 2011. Т. 88, № 4. С. 132. [Doroshenkova A.E., Stavitskaya N.V. Genetic characteristics of children with different forms of pulmonary tuberculosis. Tuberkulez i bolezni legkikh = Tuberculosis and Lung Disease, 2011, Vol. 88, no. 4, p. 132. (In Russ.)]

8. Frodsham A.J., Hill A.V.S. Genetic of infections disease. Hum. Mol.Genet., 2004, Vol. 69, рр.187-194.