Адрес для переписки:Шабалдин Андрей Владимирович ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний» 652002, Россия, г. Кемерово, Сосновый бульвар, 6. Тел.: 8 (903) 907-51-97.

Background. LeggCalvePerthes disease (LCPD) is an idiopathic avascular femoral head osteonecrosis. The early disease stage is associated with the development of synovitis of the hip joint linked to the overproduction of factors induced by hypoxia as well as of interleukin (IL)-6. Associations of individual polymorphic variants of cytokine genes with LCPD have been shown. Moreover, alterations in the cytokine regulatory cascade are considered an important link in the pathogenesis of synovial inflammation in the early stages of LCPD. Accordingly, this process may be associated with a certain combination of polymorphic variants of the genes for pro-inflammatory and anti-inflammatory cytokines. Aim. This study aimed to study the associations of polymorphic variants of the genes for pro-inflammatory and anti-inflammatory IL with LCPD. Materials and methods. In this casecontrol study, the main and control groups were composed of 26 children with LCPD and 40 healthy children (all aged 311 years), respectively. Genotyping of IL10 (rs1800896), IL13 (rs20541), IL18 (rs187238), IL18 (rs5744292), IL1a (rs1800587), IL1RA (POL_GF_58), IL-1Ra (rs4251961), IL1B (rs16944), IL1B (rs1143634), IL4 (POL_GF_59), IL4 (rs2243250), IL6 (rs1800796), IL6 (rs1800795), INF (rs2430561), TGF (rs1800469), and TNF (rs1800629) was performed by polymerase chain reaction (PCR) using TaqMan probes to the corresponding polymorphic variants of genes produced by Thermo Fisher Scientific (USA) on an amplifier ViiATM 7 RealTime PCR System (Life Technologies, USA). Statistical processing of the results was carried out using the SNPstats program and multifactor dimensionality reduction. Results. The study revealed three separate LCPD-potentiating genotypes of polymorphic variants of cytokine genes: IL10 (rs1800896; TC)*T/C (OR 6.50), IL4 (POL_GF_49, VNTR, Intron4)*2R/2R (OR 12.32), and IL-6 (rs1800796; GC)*G/C (OR 4.08). Two polymorphic variants of the IL4 gene (POL_GF_49, VNTR, Intron4, and rs2243250; CT) had a pronounced synergism with respect to the diagnosis of LCPD. Moderate synergy with respect to the diagnosis of LCPD demonstrated the intergenic interaction of IL6 (rs1800796, GC) with tumor necrosis factor- (rs1800629, GA). Moderate antagonism between LCPD and intergenic interactions was obtained for polymorphic variants of IL18 (rs5744292, TC) and transforming growth factor- (rs1800469, AG) genes. Conclusions. The pathogenesis of synovitis and subsequent osteonecrosis in LCPD is associated with a combination of polymorphic variants of the genes of pro-inflammatory and anti-inflammatory cytokines, as well as of DNA variants of the pro-allergic IL4 gene.

Адрес для переписки:Шабалдин Андрей Владимирович 650002, Россия, Кемерово, Сосновый бульвар, 6, ФГБНУ НИИ комплексных проблем сердечно-сосудистых заболеваний. Тел.: (3842) 39-64-29 (служебн.); 8 951 163-90-11 (моб.). E-mail: weit2007@ya.ru Contacts:Andrey V. Shabaldin 650002, Russian Federation, Kemerovo, Sosnovy blvd., 6, Scientific Research Institute for Complex Issues of Cardiovascular Diseases. Phone: +7 (3842) 39-64-29 (office); +7 951 163-90-11 (mobile). E-mail: weit2007@ya.ru Библиографическое описание: Шабалдин А.В., Шабалдина Е.В., Рязанцев С.В., Симбирцев А.С. Полиморфизм генов семейства интерлейкина 1 и интерлейкина 4 при сенсибилизации детей раннего и дошкольного возраста к Streptococcus pyogenes // Инфекция и иммунитет. 2016. Т. 6, № 1. С. 45-54. doi: 10.15789/2220-7619-2016-1-45-54 Citation: Shabaldin A.V., Shabaldina E.V., Ryazantsev S.V., Simbirtsev A.S. Interleukin 1 and interleukin 4 genes polymorphism associated with early and preschool age children sensitization to Streptococcus pyogenes // Russian Journal of Infection and Immunity = Infektsiya i immunitet, 2016, vol. 6, no. 1, pp. 45-54. doi: 10.15789/2220-7619-2016-1-45 Резюме. Введение. Инфицирование Streptococcus pyogenes и сенсибилизация к его антигенам является небла-гоприятным фактором в отношении индукции ревматической патологии. Поиск генетических предикторов ревматической патологии в целом и сенсибилизации к S. pyogenes в частности является актуальной пробле-мой современной медицины. Цель: изучение ассоциативных связей между полиморфизмами генов семейства интерлейкина 1 и интерлейкина 4 и развитием сенсибилизации к антигенам S. pyogenes у детей раннего и до-школьного возраста. Материалы и методы. Проведено обследование 771 ребенка, в возрастном интервале 2-6 лет, проходивших лечение по поводу рецидивирующих острых респираторных инфекций у врачей ал-лерголога-иммунолога и оториноларинголога. Всем детям проводили исследование антител к S. pyogenes с по-мощью твердофазного иммуноферментного анализа на к оммерческих наборах ООО «Иммунотекс» (г. Став-рополь, Россия). Детей, имеющих иммунный ответ по IgG типу к S. pyogenes, относили к основной группе (n = 306), а не имеющих его -к контрольной группе (n = 465 (+3953, С→T)*C,C / IL1Ra (VNTR, intron 2, 89 bp)*2r,4r / IL4 (VNTR intron 3, 70 bp)*2r,2r (OR = 46,15); IL1B (+3953, С→T)*T,T / I-1Ra (VNTR, intron 2, 89 bp)*4r,4r / IL4 (VNTR 46Инфекция и иммунитет А.В. Шабалдин и др. (OR = 7,23 Abstract. Background. Streptococcus pyogenes infection and sensitization to its antigens is considered to be an unfavorable factor for the induction of rheumatic pathology. The search for genetic predictors of rheumatic diseases in general, and sensitization to S. pyogenes, in particular, is of high relevance in modern medicine. Objective. To study the associations between interleukin 1 and interleukin 4 gene polymorphisms and the development of sensitization to antigens of S. pyogenes in toddlers and preschool children. Materials and methods. 771 children aged 2-6 years with recurrent acute respiratory...

BACKGROUND: The problem of anti-shock measures and stabilization of the general condition of the affected children with polytrauma at the stage of intensive care is an extremely urgent issue in pediatric traumatology. Various aspects, such as determining the most sensitive prognostic scale for assessing the severity of polytrauma, clinical and laboratory predictors of changes in the vector of development of the course of traumatic disease in the direction of thanatogenic orientation, remain actively discussed among clinicians. АIM: The aim of the study is to analyse the dynamics of changes in the indicators of internal homeostasis in children with polytrauma, indicating a favorable or thanatogenic direction of the course of the traumatic disease. MATERIALS AND METHODS: A retrospective analysis of the medical records of 49 patients diagnosed with polytrauma was performed. All patients were divided into two groups: the survivors group comprised 41 patients, and the deceased group consisted of 8 patients. All patients were examined for total blood count (Er, Tr, Ht, Hb, le, ESR), acid-base state (pH, SBC, BE), blood biochemical parameters (creatinine, urea, ALT, AST, K, Na, Ca), and C-reactive protein. The tests were performed daily during the first 10 days of the acute phase of the injury. The severity of the injury was determined by the NISS and pediatric trauma score scales, and in the case of a traumatic brain injury, the Glasgow coma scale was used. A logistic step-by-step regression analysis was performed to identify predictors of polytrauma outcomes. The statical significance was considered at p 0.05. RESULTS: The step-by-step logistic regression revealed significant predictors that determined the unfavorable outcome of polytrauma (death), already on the second day. They were the NISS score, the level of CRP, Hb, Er, Na, and creatinine. At the same time, the statistical significance in the dynamics of changes in red blood parameters (Er, Hb), blood ionic composition (Na, K), humoral activity (Le, ESR, CRP) remained up to 10 days, i.e., during the period of possible complications of the traumatic disease. Our data offered the possibility to derive an equation for calculating the risk of failure of compensatory mechanisms in polytrauma. CONCLUSIONS: The course of traumatic disease in children with polytrauma is characterized by morpho-functional changes in many organ systems. Predictors of failure of compensatory-adaptive mechanisms in response to polytrauma can be determined already in the early post-shock period.