jofinЖурнал инфектологииJournal Infectology2072-6732IPO “АIDSSPbR"10.22625/2072-6732-2019-11-4-72-78jofin-964Research ArticleОригинальные исследованияOriginal ResearchРоль генодиагностики в прогнозировании ДВС-синдрома и риска развития полиорганной недостаточности у детей с генерализованными формами менингококковой инфекцииRole of genotyping in prediction of disseminated intravascular coagulation and multiple organ failure in children with generalized forms of meningococcal infectionКапустинС. И.KapustinS. I.

Капустин Сергей Игоревич - руководитель лаборатории биохимии, доктор биологических наук.

Saint-Petersburg

kapustin.sergey@mail.ruВильницА. А.VilnitsA. A.

Вильниц Алла Ароновна - старший научный сотрудник отдела нейроинфекций и органической патологии нервной системы, кандидат медицинских наук.

Saint-Petersburg

vilnitz@mail.ruСидороваЖ. Ю.SidorovaZh. Yu.

Сидорова Жанна Юрьевна - старший научный сотрудник лаборатории биохимии, кандидат биологических наук

Saint-Petersburg

sidorovajanet@gmail.comЧеботкевичВ. Н.ChebotkevichV. N.

Чеботкевич Виталий Николаевич - руководитель лаборатории бактериологии, доктор медицинских наук, профессор.

Saint-Petersburg

vitnikcheb@mail.ruПапаянЛ. П.PapayanL. P.

Папаян Людмила Петровна - руководитель лаборатории свертывания крови, доктор медицинских наук, профессор.

Saint-Petersburg

papayan@mail.ruАлексееваЛ. А.AlekseevaL. A.

Алексеева Лидия Аркадиевна - руководитель отдела клинической лабораторной диагностики, ведущий научный сотрудник, доктор биологических наук

Saint-Petersburg

kldidi@mail.ruСкрипченкоН. В.SkripchenkoN. V.

Скрипченко Наталия Викторовна - заместитель директора по научной работе, доктор медицинских наук, профессор, заслуженный деятель науки РФ.

Saint-Petersburg

snv@niidi.ruБессмельцевС. С.BessmeltsevS. S.

Бессмельцев Станислав Семенович - заместитель директора по научной работе, доктор медицинских наук, профессор.

Санкт-Петербург, тел.: 8(812)717-67-80

Saint-Petersburg

bsshem@hotmail.comРоссийский научно-исследовательский институт гематологии и трансфузиологииРоссияRussian Research Institute of hematology and transfusiologyRussian FederationДетский научно-клинический центр инфекционных болезнейРоссияPediatric Research and Clinical Center for Infectious DiseasesRussian Federation2019071220191147278Copyright © Капустин С.И., Вильниц А.А., Сидорова Ж.Ю., Чеботкевич В.Н., Папаян Л.П., Алексеева Л.А., Скрипченко Н.В., Бессмельцев С.С., 20192019Капустин С.И., Вильниц А.А., Сидорова Ж.Ю., Чеботкевич В.Н., Папаян Л.П., Алексеева Л.А., Скрипченко Н.В., Бессмельцев С.С.Kapustin S.I., Vilnits A.A., Sidorova Z.Y., Chebotkevich V.N., Papayan L.P., Alekseeva L.A., Skripchenko N.V., Bessmeltsev S.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.niidi.ru/jofin/article/view/964Цель

Цель: изучить особенности аллельного полиморфизма ряда генов иммунной системы, и гемостаза у детей с генерализованными формами менингококковой инфекции и оценить возможность использования результатов генотипирования для прогнозирования тяжелого течения ДВС-синдрома и развития полиорганной недостаточности (ПОН).

Материалы, и методы

Материалы, и методы.: обследовано 20 детей в возрасте от. 8 месяцев до 17 лет. с генерализованными формами менингококковой инфекции, протекающими с синдромом. ПОН или/и тромбогеморрагическими нарушениями. Контрольную группу составили 200 доноров крови. В качестве материала исследования использована геномная ДНК, выделенная из лейкоцитов периферической крови. Выявление аллельных вариантов генов, ассоциированных с дисфункцией плазменного звена гемостаза (FI-A, FI-B, FXIII-A, PAI-1, ТРА) и повышенной продукцией ряда провоспалительных цитокинов (IL-6, IL-1B, TNF-A), проводили с помощью полимеразной цепной реакции и последующего рестрикционного анализа. Частоты встречаемости аллелей и генотипов определялись прямым подсчетом. Межгрупповые различия в распределении аллелей и генотипов оценивались с помощью точного метода Фишера. Статистическая обработка проводилась с использованием программы GraphPadPrism, версия 4.0.

Результаты

Результаты: в группе детей с генерализованными формами менингококковой инфекции доля гетерозигот, по полиморфизму 174 G/C в гене IL-6 была в 1,5 раза выше, чем. в контроле (75,0% против 50,0% соответственно, OR=3,0; 95% CI: 1,1-8,6; p=0,037). Генотип ТРА Del/Del встречался в группе детей с ПОН в 4 раза чаще, чем у пациентов с относительно благоприятным течением заболевания (45,4% против 11,1% соответственно, OR=6,7; 95% CI: 0,6-73,1; p=0,16). Выявлено увеличение в группе детей с ПОН доли лиц, имеющих в генотипе два и более неблагоприятных варианта изученных генов (р=0,022).

Заключение

Заключение: комплексная оценка аллельного полиморфизма 8 генов плазменных факторов гемостаза и провоспалительных цитокинов позволяет, с высокой долей достоверности определить группу риска по развитию ПОН среди детей с генерализованными бактериальными инфекциями. Генотип ТРА Del/Del может, являться неблагоприятным, маркером, при данной патологии и быть ассоциированным, с высоким, риском, развития тяжелого ДВС-синдрома.

Aim

Aim: To investigate the features of allelic polymorphism, of several immune- and hemostasis-related genes in children with generalized, meningococcal infections and. to assess the usefulness of genotyping for prediction, of severe disseminated intravascular coagulation (DIC) and. multiple organ dysfunction, syndrome in these patients.

Materials and methods

Materials and methods: we studied. 20 children aged, from 8 months up to 17 years with generalized, meningococcal infections who developed DIC or/and multiple organ dysfunction syndrome. The control group consisted, of 200 blood, donors. Genomic DNA was isolated, from peripheral blood, leucocytes. Allelic variants of genes coding for plasma hemostatic factors (FI-A, FI-B, FXIII-A, PAI-1, ТРА) or pro-inflammatory cytokines (IL-6, IL-1B, TNF-A) were detected by PCR and. subsequent restriction, analysis. Allele and. genotype frequencies were calculated, by direct counting, and. their differences between the groups were assessed, by Fisher's exact test. For statistical analysis, the GraphPad. Prism, ver.4.0 software was used.

Results

Results: in the group of children with generalized, meningococcal infections, the frequency of heterozygotes for the IL-6 -174 G/C polymorphism, was 1.5-fold higher than in the controls (75.0% vs. 50.0%, respectively, OR=3.0; 95% CI: 1.1-8.6; p=0.037). Genotype TPA Del/Del was detected 4-fold more frequently in children who developed multiple organ dysfunction syndrome than in those with the more favorable disease course (45.4% vs. 11.1%, respectively, OR=6.7; 95% CI: 0.6-73.1; p=0.16). Moreover, among the patients having multiple organ dysfunction, syndrome, we observed, more frequently individuals who possessed, at least 2 unfavorable genetic variants (p=0.022).

Conclusion

Conclusion: Simultaneous assessment of nucleotide variations in 8 studied genes could help to define the group of children with high, risk of multiple organ dysfunction, syn-drome.Genotype TPA Del/Del, associated, with decreased, production, of this factor, might serve as a marker of unfavorable DIC course and possible predictor of multiple organ dysfunction. syndrome in children with generalized, meningpcoc-cal infections.

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The authors declare that there are no conflicts of interest present.