rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2019-3-48-60rmt-1775Research ArticleКЛИНИЧЕСКАЯ ПРАКТИКАCLINICAL PRACTICEРастворимая форма триггерного рецептора миелоидных клеток-1 (sTREM-1) и полиморфные варианты TREM-1 при развитии полиорганной недостаточности после операции коронарного шунтированияSoluble triggering receptor expressed on myeloid cells 1 (sTREM-1) and polymorphic variants of TREM-1 in the development of multiple organ dysfunction syndrome after coronary artery bypass graftingХуторнаяМ. В.KhutornyaM. V.

650002, г. Кемерово, Сосновый бульвар, д. 6

6 Sosnovy bulvar, 650002 Kemerovo

masha_hut@mail.ruПонасенкоА. В.PonasenkoA. V.

650002, г. Кемерово, Сосновый бульвар, д. 6

6 Sosnovy bulvar, 650002 Kemerovo

ЦепокинаА. В.TsepokinaA. V.

650002, г. Кемерово, Сосновый бульвар, д. 6

6 Sosnovy bulvar, 650002 Kemerovo

РадивилкоА. С.RadivilkoA. S.

650002, г. Кемерово, Сосновый бульвар, д. 6

6 Sosnovy bulvar, 650002 Kemerovo

ЖидковаИ. И.ZhidkovaI. I.

650002, г. Кемерово, Сосновый бульвар, д. 6

6 Sosnovy bulvar, 650002 Kemerovo

КутихинА. Г.KutikhinA. G.

650002, г. Кемерово, Сосновый бульвар, д. 6

6 Sosnovy bulvar, 650002 Kemerovo

КрутицкийС. С.KrutitskyS. S.

650002, г. Кемерово, Сосновый бульвар, д. 6

6 Sosnovy bulvar, 650002 Kemerovo

ГоловкинА. С.GolovkinA. S.

197341, г. Санкт-Петербург, ул. Аккуратова, д. 2

2 Akkuratova Str., 197341 Saint Petersburg

ГригорьевЕ. В.GrigorievE. V.

650002, г. Кемерово, Сосновый бульвар, д. 6

6 Sosnovy bulvar, 650002 Kemerovo

НИИ комплексных проблем сердечно-сосудистых заболеванийРоссияResearch Institute of complex problems of cardiovascular diseaseRussian FederationНациональный медицинский исследовательский центр им. В. А. Алмазова Минздрава РоссииРоссияV. A. Almazov National Medical Research Center, Ministry of Health of RussiaRussian Federation2019060720191534860Copyright © Хуторная М.В., Понасенко А.В., Цепокина А.В., Радивилко А.С., Жидкова И.И., Кутихин А.Г., Крутицкий С.С., Головкин А.С., Григорьев Е.В., 20192019Хуторная М.В., Понасенко А.В., Цепокина А.В., Радивилко А.С., Жидкова И.И., Кутихин А.Г., Крутицкий С.С., Головкин А.С., Григорьев Е.В.Khutornya M.V., Ponasenko A.V., Tsepokina A.V., Radivilko A.S., Zhidkova I.I., Kutikhin A.G., Krutitsky S.S., Golovkin A.S., Grigoriev E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.reanimatology.com/rmt/article/view/1775

Появление тяжелых осложнений в виде полиорганной недостаточности (ПОН) после операций коронарного шунтирования (КШ) является результатом тяжелой стресс-реакции организма. Ключевым этиопатологическим фактором индукционной фазы комплексного патологического процесса, приводящего, в конечном счете, к нарушению функции органов и систем, является нарушение функций иммунного реагирования. Особенности реакций иммунной системы у конкретного индивидуума в определенной степени обусловлены генетически и реализуются через активацию врожденного иммунитета.

Цель исследования

Цель исследования: определить значение полиморфизма гена TREM-1 в связи с изменением сывороточных концентраций sTREM и их вклад в развитие полиорганной недостаточности у пациентов после операции коронарного шунтирования.

Материалы и методы

Материалы и методы. В исследование включили 132 пациента с атеросклерозом коронарных артерий, перенесших операцию коронарного шунтирования. Ранний послеоперационный период у 30 из них осложнился развитием полиорганной недостаточности. Концентрацию sTREM в сыворотке крови определяли методом иммуноферментного анализа. Генотипирование полиморфных сайтов гена TREM-1 осуществляли методом аллель-специфичной ПЦР в реальном времени по технологии TaqMan.

Результаты

Результаты. В результате исследования обнаружили статистически значимые различия в концентрациях sTREM у пациентов с ПОН и пациентов без осложнений. Установили, что концентрация sTREM зависит от носительства определенных аллельных вариантов в трех полиморфных сайтах гена TREM-1 (rs1817537, rs2234246, rs3804277)

Заключение

Заключение. В данной работе впервые определили взаимосвязь концентраций циркулирующей растворимой формы TREM-1 и полиморфных вариантов кодирующего гена TREM-1 с выраженностью ПОН у пациентов с ишемической болезнью сердца (ИБС) в послеоперационном периоде КШ.

The onset of critical complications (multiple organ dysfunction syndrome, MODS) after coronary artery bypass grafting is the result of severe stress response. The key etiopathological factor of the induction phase of the complex pathological process, which ultimately leads to dysfunction of organs and systems, is the dysfunction of the immune response. The characteristics of reactions of the immune system in a particular individual are genetically determined and realized through innate immunity activation. 

Aim

Aim. To determine the role of TREM-1 gene polymorphism through the changes of sTREM serum levels and their contribution to the development of multiple organ dysfunction syndrome after coronary artery bypass grafting.

Materials and Methods

Materials and Methods. 132 patients with coronary atherosclerosis who had undergone coronary artery bypass grafting were included in the study. Of them, 30 patients had multiple organ dysfunction syndrome in the early postoperative period. sTREM serum levels were measured using enzyme immunoassay. Genotyping of polymorphic loci of the TREM-1 gene was performed with real-time allele-specific PCR using TaqMan system.

Results

Results. Significant differences in sTREM levels among patients with and without MODS were found. sTREM levels depend on the carriage of certain allelic variants in the three polymorphic loci of the TREM-1 gene (rs1817537, rs2234246, rs3804277)

Conclusion

Conclusion. The relationships of the levels of the circulating soluble form of TREM-1 and the polymorphic variants of the coding TREM-1 gene with the severity of MODS were determined in coronary artery disease patients after coronary artery bypass grafting. 

ишемическая болезнь сердцаполиорганная недостаточностькоронарное шунтированиеврожденный иммунитетTREM-1coronary artery diseasemultiple organ dysfunction syndromecoronary artery bypass graftinginnate immunityTREM-1ReferencesHatakeyama N., Matsuda N. Alert cell strategy: mechanisms of inflammatory response and organ protection. Curr Pharm Des. 2014; 20 (36): 5766-5778. DOI: 10.2174/138161282036140912122809Hatakeyama N., Matsuda N. Alert cell strategy: mechanisms of inflammatory response and organ protection. Curr Pharm Des. 2014;20 (36): 5766-5778. DOI: 10.2174/138161282036140912122809Барбараш Л. С., Григорьев Е. В., Плотников Г. П., Хаес Б. Л., Моисеенков Г. В., Шукевич Д. Л., Иванов С. В., Одаренко Ю. Н. Полиорганная недостаточность после кардиохирургических вмешательств. Общая реаниматология. 2010; 6 (5): 31-35. DOI: 10.15360/1813-9779-2010-5-31Barbarash L.S., Grigoryev E.V., Plotnikov G.P., Khaes B.L., Moiseyenkov G.V., Shukevich D.L., Ivanov S.V., Odarenko Yu.N. Multiple organ dysfunction after cardiosurgical interventions. Obshchaya Reanimatologiya = General Reanimatology. 2010; 6 (5): 31-34. DOI: 10.15360/18139779-2010-5-31. DOI: 10.15360/1813-9779-2010-5-31[In Russ].Гусев Е.Ю., Черешнев В.А., Юрченко Л.Н. Системное воспаление с позиции теории типового патологического процесса. Цитокины и воспаление. 2007;6 (4): 9-21.Gusev E.Yu., Chereshnev V.A., Yurchenko L.N. Systemic inflammation from the standpoint of the theory of a typical pathological process. Tsitokiny i Vospalenie. 2007; 6 (4): 9-21. [In Russ]Golovkin A. S., Matveeva V. G., Kudryavtsev I. V., Chernova M. N., Bayrakova Y. V., Shukevich D. L., Grigoriev E. V. Perioperative dynamics of TLR2, TLR4, and TREM-1 expression in monocyte subpopulations in the setting of on-pump coronary artery bypass surgery. ISRN inflammation, 2013.Golovkin A. S., Matveeva V. G., Kudryavtsev I. V., Chernova M. N., Bayrakova Y. V., Shukevich D. L., Grigoriev E. V. Perioperative dynamics of TLR2, TLR4, and TREM-1 expression in monocyte subpopulations in the setting of on-pump coronary artery bypass surgery. ISRN inflammation, 2013.Iwasaki A., Medzhitov R. Control of adaptive immunity by the innate immune system. Nat Immunol. 2015;16 (4): 343-353. DOI: 10.1038/ni.3123.Iwasaki A., Medzhitov R. Control of adaptive immunity by the innate immune system. Nat Immunol. 2015;16 (4): 343-353. DOI: 10.1038/ni.3123.Хуторная М. В., Понасенко А. В., Головкин А. С. Триггерный рецептор экспрессируемый на миелоидных клетках (TREM-1): генетический полиморфизм и роль в реализации иммунного ответа. Медицина в Кузбассе. 2013;12 (4): 14-18.Khutornaya M.V., Ponasenko A.V., Golovkin A.S. Trigger receptor expressed on myeloid cells (TREM-1): genetic polymorphism and role in the implementation of the immune response.. Meditsina v Kuzbasse. 2013; 12 (4): 14-18. [In Russ]Vincent J-L., Moreno R., Takala J., Willatts S., De Mendonça A., Bruining H., Reinhart C.K., Suter P.M., Thijs L.G. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996; 22 (7): 707-710Vincent J-L., Moreno R., Takala J., Willatts S., De Mendonça A., Bruining H., Reinhart C.K., Suter P.M., Thijs L.G. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996; 22 (7): 707-710Scott M.C. Defining and Diagnosing Sepsis. Emerg Med Clin North Am. 2017;35 (1): 1-9. DOI: 10.1016/j.emc.2016.08.002.Scott M.C. Defining and Diagnosing Sepsis. Emerg Med Clin North Am. 2017;35 (1): 1-9. DOI: 10.1016/j.emc.2016.08.002.Smith К., Kliko С., Cantor C. Puls-elektroforez and methods of work with the big molecules of DNA. The Analysis of the genome. Methods: the Lane with English. М: World; 1990:58-94.Smith К., Kliko С., Cantor C. Puls-elektroforez and methods of work with the big molecules of DNA. The Analysis of the genome. Methods: the Lane with English. М: World; 1990:58-94.Blumenthal M.N., Namboodiri K., Mendell N., Gleich G., Elston R.C., Yunis E. Genetic transmission of serum IgE Levels. Am J Med Genet.1981;10 (3): 219-228. DOI: 10.1002/ajmg.1320100304Blumenthal M.N., Namboodiri K., Mendell N., Gleich G., Elston R.C., Yunis E. Genetic transmission of serum IgE Levels. Am J Med Genet.1981;10 (3): 219-228. DOI: 10.1002/ajmg.1320100304Gibot S., Cravoisy A., Levy B., Béné M.C., Faure G., Bollaert P.E. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med. 2004; 350 (5): 451–458. DOI: 10.1056/NEJMoa031544Gibot S., Cravoisy A., Levy B., Béné M.C., Faure G., Bollaert P.E. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med. 2004; 350 (5): 451–458. DOI: 10.1056/NEJMoa031544Liu C.L., Hsieh W.Y., Wu C.L., Kuo H.T., Lu Y.T. Triggering receptor expressed on myeloid cells-1 in pleural effusions: a marker of inflammatory disease. Respir Med. 2007; 101 (5): 903–909. DOI: 10.1016/j.rmed.2006.09.021Liu C.L., Hsieh W.Y., Wu C.L., Kuo H.T., Lu Y.T. Triggering receptor expressed on myeloid cells-1 in pleural effusions: a marker of inflammatory disease. Respir Med. 2007; 101 (5): 903–909. DOI: 10.1016/j.rmed.2006.09.021Collins C.E., La D.T., Yang H.T., Massin F., Gibot S., Faure G., Stohl W. Elevated synovial expression of triggering receptor expressed on myeloid cells 1 in patients with septic arthritis or rheumatoid arthritis. Ann Rheum Dis. 2009; 68 (11): 1768–1774. DOI: 10.1136/ard.2008.089557Collins C.E., La D.T., Yang H.T., Massin F., Gibot S., Faure G., Stohl W. Elevated synovial expression of triggering receptor expressed on myeloid cells 1 in patients with septic arthritis or rheumatoid arthritis. Ann Rheum Dis. 2009; 68 (11): 1768–1774. DOI: 10.1136/ard.2008.089557Determann R.M., Weisfelt M., de Gans J., van der Ende A., Schultz M.J. van de Beek D. Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis. Intensive Care Med 2006;32 (8): 1243–1247. DOI: 10.1007/s00134-006-0240-4Determann R.M., Weisfelt M., de Gans J., van der Ende A., Schultz M.J. van de Beek D. Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis. Intensive Care Med 2006;32 (8): 1243–1247. DOI: 10.1007/s00134-006-0240-4Kusanovic J.P., Romero R., Chaiworapongsa T., Mittal P., Mazaki-Tovi S., Vaisbuch E., Erez O., Gotsch F., Than N.G., Edwin S.S., Pacora P., Jodicke C., Yeo L., Hassan S.S. Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2010; 23 (1): 34–47. DOI: 10.3109/14767050903009248Kusanovic J.P., Romero R., Chaiworapongsa T., Mittal P., Mazaki-Tovi S., Vaisbuch E., Erez O., Gotsch F., Than N.G., Edwin S.S., Pacora P., Jodicke C., Yeo L., Hassan S.S. Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2010; 23 (1): 34–47. DOI: 10.3109/14767050903009248Determann R.M., van Till J.W., van Ruler O., van Veen S.Q., Schultz M.J., Boermeester M.A. sTREM-1 is a potential useful biomarker for exclusion of ongoing infection in patients with secondary peritonitis. Cytokine. 2009; 46 (1): 36–42. DOI: 10.1016/j.cyto.2008.12.006Determann R.M., van Till J.W., van Ruler O., van Veen S.Q., Schultz M.J., Boermeester M.A. sTREM-1 is a potential useful biomarker for exclusion of ongoing infection in patients with secondary peritonitis. Cytokine. 2009; 46 (1): 36–42. DOI: 10.1016/j.cyto.2008.12.006Su L.X., Feng L., Zhang J., Xiao Y.J., Jia Y.H., Yan P., Feng D., Xie L.X. Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study. Crit Care. 2011; 15 (5): R250. DOI: 10.1186/cc10508Su L.X., Feng L., Zhang J., Xiao Y.J., Jia Y.H., Yan P., Feng D., Xie L.X. Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study. Crit Care. 2011;15 (5): R250. DOI: 10.1186/cc10508Zhang J., She D., Feng D., Jia Y., Xie L. Dynamic changes of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflect sepsis severity and can predict prognosis: a prospective study. BMC Infect Dis. 2011, 11:53. DOI: 10.1186/1471-2334-11-53Zhang J., She D., Feng D., Jia Y., Xie L. Dynamic changes of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflect sepsis severity and can predict prognosis: a prospective study. BMC Infect Dis. 2011, 11:53. DOI: 10.1186/1471-2334-11-53Gibot S., Cravoisy A., Kolopp-Sarda M.N., Béné M.C., Faure G., Bollaert P.E., Levy B.Time-course of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis. Crit Care Med. 2005; 33 (4): 792–796. DOI: 10.1097/01.CCM.0000159089.16462.4AGibot S., Cravoisy A., Kolopp-Sarda M.N., Béné M.C., Faure G., Bollaert P.E., Levy B. Time-course of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis. Crit Care Med. 2005; 33 (4): 792–796. DOI: 10.1097/01.CCM.0000159089.16462.4ASu L., Han B., Liu C., Liang L., Jiang Z., Deng J., Yan P., Jia Y., Feng D., Xie L. Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study. BMC Infectious Diseases. 2012;12: 157. DOI: 10.1186/1471-2334-12-157Su L., Han B., Liu C., Liang L., Jiang Z., Deng J., Yan P., Jia Y., Feng D., Xie L. Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study. BMC Infectious Diseases. 2012; 12: 157. DOI: 10.1186/1471-2334-12-157Brenner T., Uhle F., Fleming T., Wieland M., Schmoch T., Schmitt F., Schmidt K., Zivkovic A.R., Bruckner T., Weigand M.A., Hofer S. Soluble TREM-1 as a diagnostic and prognostic biomarker in patients with septic shock: an observational clinical study. Biomarkers. 2017; 22 (1): 63-69. DOI: 10.1080/1354750X.2016.1204005Brenner T., Uhle F., Fleming T., Wieland M., Schmoch T., Schmitt F., Schmidt K., Zivkovic A.R., Bruckner T., Weigand M.A., Hofer S. Soluble TREM-1 as a diagnostic and prognostic biomarker in patients with septic shock: an observational clinical study. Biomarkers. 2017; 22 (1): 63-69. DOI: 10.1080/1354750X.2016.1204005Dai D., Xiong W., Fan Q., Wang H., Chen Q., Shen W., Zhang R., Ding F., Lu L., Tao R. Association of decreased serum sTREM-1 level with the severity of coronary artery disease: Inhibitory effect of sTREM-1 on TNF-α- and oxLDL-induced inflammatory reactions in endothelial cells. Medicine (Baltimore). 2016; 95 (37): е4693. DOI: 10.1097/MD.0000000000004693Dai D., Xiong W., Fan Q., Wang H., Chen Q., Shen W., Zhang R., Ding F., Lu L., Tao R. Association of decreased serum sTREM-1 level with the severity of coronary artery disease: Inhibitory effect of sTREM-1 on TNF-α- and oxLDL-induced inflammatory reactions in endothelial cells. Medicine (Baltimore). 2016;95 (37): е4693. DOI: 10.1097/MD.0000000000004693Wang F., Li C., Ding F. H., Shen Y., Gao J., Liu Z. H., Chen J. W., Zhang R. Y., Shen W. F., Wang X. Q., Lu L. Increased serum TREM-1 level is associated with in-stent restenosis, and activation of TREM-1 promotes inflammation, proliferation and migration in vascular smooth muscle cells. Atherosclerosis.2017; 267: DOI: 10.1016/j.atherosclerosis.2017.10.015Wang F., Li C., Ding F. H., Shen Y., Gao J., Liu Z. H., Chen J. W., Zhang R. Y., Shen W. F., Wang X. Q., Lu L. Increased serum TREM-1 level is associated with in-stent restenosis, and activation of TREM-1 promotes inflammation, proliferation and migration in vascular smooth muscle cells. Atherosclerosis.2017; 267: DOI: 10.1016/j.atherosclerosis.2017.10.015Oku R., Oda S., Nakada T.A., Sadahiro T., Nakamura M., Hirayama Y., Abe R., Tateishi Y., Ito M., Iseki T., Hirasawa H. Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS. Cytokine. 2013;61 (1): 112-117. DOI: 10.1016/j.cyto.2012.09.003Oku R., Oda S., Nakada T.A., Sadahiro T., Nakamura M., Hirayama Y., Abe R., Tateishi Y., Ito M., Iseki T., Hirasawa H. Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS. Cytokine. 2013;61 (1): 112-117. DOI: 0.1016/j.cyto.2012.09.003Rivera-Chavez F.A., Minei J.P. Soluble triggering receptor expressed on myeloid cells-1 is an early marker of infection in the surgical intensive care unit.Surg Infect (Larchmt). 2009; 10 (5): 435–439. DOI: 10.1089/sur.2009.030Rivera-Chavez F.A., Minei J.P. Soluble triggering receptor expressed on myeloid cells-1 is an early marker of infection in the surgical intensive care unit.Surg Infect (Larchmt). 2009; 10 (5): 435–439. DOI: 10.1089/sur.2009.030Su L., Liu C., Li C., Jiang Z., Xiao K., Zhang X., Li M., Yan P., Feng D., Xie L. Dynamic changes in serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and its gene polymorphisms are associated with sepsis prognosis. Inflammation. 2012; 35 (6): 18331843. DOI: 10.1007/s10753-012-9504-zSu L., Liu C., Li C., Jiang Z., Xiao K., Zhang X., Li M., Yan P., Feng D., Xie L. Dynamic changes in serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and its gene polymorphisms are associated with sepsis prognosis. Inflammation. 2012; 35 (6): 18331843. DOI: 10.1007/s10753-012-9504-zAldasoro Arguinano A.A., Dadé S., Stathopoulou M., Derive M., Coumba Ndiaye N., Xie T., Masson C., Gibot S., Visvikis-Siest S. TREM-1 SNP rs2234246 regulates TREM-1 protein and mRNA levels and is associated with plasma levels of L-selectin. PLoS One. 2017;12 (8): e0182226. DOI: 10.1371/journal.pone.Aldasoro Arguinano A.A., Dadé S., Stathopoulou M., Derive M., Coumba Ndiaye N., Xie T., Masson C., Gibot S., Visvikis-Siest S. TREM-1 SNP rs2234246 regulates TREM-1 protein and mRNA levels and is associated with plasma levels of L-selectin. PLoS One. 2017;12 (8): e0182226. DOI: 10.1371/journal.pone.Charles P.E., Noel R., Massin F., Guy J., Bollaert P.E., Quenot J.P., Gibot S. Significance of soluble triggering receptor expressed on myeloid cells1 elevation in patients admitted to the intensive care unit with sepsis. BMC Infect Dis.. 2016;16 (1): 559. DOI: 10.1186/s12879-016-1893-4Charles P.E., Noel R., Massin F., Guy J., Bollaert P.E., Quenot J.P., Gibot S. Significance of soluble triggering receptor expressed on myeloid cells1 elevation in patients admitted to the intensive care unit with sepsis. BMC Infect Dis. 2016;16 (1): 559. DOI: 10.1186/s12879-016-1893-4

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