Impact of lymphocyte therapy on blood fibrinolytic activity and immune responses in patients with a history of reproductive losses


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To investigate the impact of lymphocyte immunotherapy on the level of cytokines (tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10), fibrinolytic responses (PAI-I level and activity, t-PA antigen, plasminogen levels, Factor XII-dependent f ibrinolysis time), and pregnancy course and outcomes. Subjects and methods. A prospective cohort study was conducted in 233 patients, including 69 pregnant women with recurrent miscarriage who had received lymphocyte immunotherapy, 73 women with recurrent miscarriage who had conventional treatment, and 91 gynecologically healthy patients. Cytokine levels and fibrinolytic indicators were determined at 7-8 weeks of gestation. Results. Immunochemotherapy increases the activity of the regulatory cytokine IL-10 (p=0.0001), reduces the proinflammatory cytokine response of TNF-α (p=0.0001) and the level (p=0.0001) and activity (p=0.0173) of PAI-1, and raises the content of t-PA (p=0.0413), without changing the integral indicator (Factor XIIa-dependent fibrinolysis). Lymphocyte therapy declines the number of fetal growth retardation cases by 2.5 times (p < 0.05). Conclusion. Therapy with allogeneic lymphocytes from the partner can be regarded as prevention of late pregnancy complications.

Full Text

Restricted Access

About the authors

Mariya Gennad’evna Nikolaeva

Altai State Medical University, Ministry of Health of Russia

Email: nikolmg@yandex.ru

Galina Valentinovna Serdyuk

Altai State Medical University, Ministry of Health of Russia

Email: Gvser@mail.ru
MD, senior researcher of laboratory of hematology

Tatiana Ivanovna Gorbacheva

Altai State Medical University, Ministry of Health of Russia

Email: tg72@bk.ru
candidate of medical sciences, associate professor in the Obstetrics and Gynecology Department

Natalya Ilyinichna Fadeeva

Altai State Medical University, Ministry of Health of Russia

Email: nat2fad@hotmail.com
M. D., Professor, head of the department of obstetrics and gynecology

Andrey Pavlovich Momot

Altai Branch, Hematology Research Center, Ministry of Health of Russia

Email: xyzam@yandex.ru
MD, Professor, Director

References

  1. Говалло В.И., Сидельникова В.М. Иммунизация беременных женщин аллогенными лимфоцитами мужа как метод профилактики самопроизвольных выкидышей. Акушерство и гинекология. 1983; 2: 25-6. [Govallo V.I., Sidelnikova V.M. Immunization of pregnant women allogeneic lymphocytes husband as a method of prevention of miscarriage. Akusherstvo i Ginekologiya/ Obstetrics and Gynecology. 1983; (2): 25-6. (in Russian)]
  2. Daya S., Gunby J. The effectiveness of allogeneic leukocyte immunization in unexplained primary recurrent spontaneous abortion. Recurrent Miscarriage Immunotherapy Trialists Group. Am. J. Reprod. Immunol. 1994; 32(4): 294-302.
  3. Khonina N.A., Broitman E.V., Shevela E.Y., Pasman N.M., Chernykh E.R. Mixed lymphocyte reaction blocking factors (MLR-Bf) as potential biomarker for indication and efficacy of paternal lymphocyte immunization in recurrent spontaneous abortion. Arch. Gynecol. Obstet. 2013; 288(4): 933-7. doi: 10.1007/ s00404-013-2832-x.
  4. Wu L., Luo L.H., Zhang Y.X., Li Q., Xu B., Zhou G. et al. Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy. Reprod. Biol. Endocrinol. 2014; 12: 74. doi: 10.1186/1477-7827-12-74. Available at: http://rbej.biomedcentral.com/ articles/10.1186/1477-7827-12-74 Accessed 27 April 2016.
  5. Cavalcante M.B., Costa Fda S., Araujo Jünior E., Barini R. Risk factors associated with a new pregnancy loss and perinatal outcomes in cases of recurrent miscarriage treated with lymphocyte immunotherapy. Mononuclear cell immunization in prevention of recurrent miscarriages: a randomized trial. J. Matern. Fetal Neonatal Med. 2015; 28(9): 1082-6. doi: 10.3109/14767058.2014.943175.
  6. Кречетова Л.В., Тетруашвили Н.К., Вторушина В.В., Степанова Е.О., Николаева М.А., Голубева Е.Л., Хачатрян Н.А. Динамика субпопуляционного состава лимфоцитов периферической крови в первом триместре беременности у женщин с привычным выкидышем на фоне проведения иммуноцитотерапии. Акушерство и гинекология. 2015; 6: 59-66. [Krechetova L.V., Tetruashvili N.K., Vtorushina V.V., Stepanova E.O., Nikolaeva M.A., Golubeva E.L., Khachatryan N.A. Time course of changes in the subpopulation composition of peripheral blood lymphocytes in the first trimester of pregnancy in women with recurrent miscarriage during immunocytotherapy. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2015; (6): 59-66. (in Russian)]
  7. Ober C., Karrison T., Odem R.R., Barnes R.B., Branch D. W., Stephenson M.D. et al. Mononuclear cell immunization in prevention of recurrent miscarriages: a randomized trial. Lancet. 1999; 354(9176): 365-9.
  8. Scott J.R. Immunotherapy for recurrent miscarriage. Cochrane Database Syst. Rev. 2000; (2): CD000112.
  9. Scott J.R. Immunotherapy for recurrent miscarriage. Cochrane Database Syst. Rev. 2003; (1): CD000112.
  10. Porter T.F., LaCoursiere Y., Scott J.R. Immunotherapy for recurrent miscarriage. Cochrane Database Syst. Rev. 2006; (2): CD000112.
  11. Wong L.F., Porter T.F., Scott J.R. Immunotherapy for recurrent miscarriage. Cochrane Database Syst. Rev. 2014; (10): CD000112. doi: 10.1002/14651858. CD000112.pub3.
  12. Gharesi-Fard B., Zolghadri J., Haghbin H. Soluble CD30 (sCD30) and effectiveness of leukocyte therapy in recurrent pregnancy loss patients. J. Reprod. Immunol. 2013; 97(2): 240-4. doi: 10.1016/j.jri.2012.11.004.
  13. Moffett A., Shreeve N. First do no harm: uterine natural killer (NK) cells in assisted reproduction. Hum. Reprod. 2015; 30(7): 1519-25. doi: 10.1093/humrep/dev098.
  14. Carp Hovard J.A., ed. Recurrent pregnancy loss: causes, controversies and treatment. 2-nd ed. London: CRC Press; 2014. 456p.
  15. Линник А.П., Буянова С.Н., Яздовский В.В., Москалец О.В., Кадашева О.Г., Иванова О.Г., Макарков А.И. Иммуноэндокринные взаимоотношения у беременных с привычным невынашиванием беременности в анамнезе. Российский вестник акушера-гинеколога. 2013; 13(2): 4-7. [Linnik A.P., Buyanova S.N., Yazdovskiy V.V., Moskalets O.V., Kadasheva O.G., Ivanova O.G., Makarkov A.I. Immunoendokrinnye relationship in women with recurrent miscarriage in anamnesis. Rossiyskiy vestnik akushera-ginekologa. 2013; 13(2): 4-7. (in Russian)]
  16. Останин А.А., Кустов С.М., Тыринова Т.В., Тихонова М.А., Хонина Н.А., Пасман Н.М., Черных Е.Р. Показатели иммунитета беременных в раннем прогнозе развития фетоплацентарной недостаточности. Акушерство и гинекология. 2010; 1: 33-8. [Ostanin A.A., Kustov S.M., Tyrinova T.V., Tikhonova M.A., Khonina N.A., Pasman N.M., Chernyh E.R. Indicators of immune pregnant women in the early prediction of placental insufficiency. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2010; (1): 33-8. (in Russian)]
  17. Газиева И.А., Чистякова Г.Н., Ремизова И.И. Роль нарушений продукции цитокинов в генезе плацентарной недостаточности и ранних репродуктивных потерь. Медицинская иммунология. 2014; 16(6): 539-50. doi: 10.15789/1563-0625-2014-6-539-550. [Gazieva I.A., Chistyakova G.N., Remizova I.I. The role of cytokine production disturbances in the genesis of the placental insufficiency and early reproductive losses. Meditsinskaya immunologiya. 2014; 16(6): 539-50. doi: 10.15789/1563-0625-2014-6-539-550. (in Russian)]
  18. Сухих Г.Т., Ванько Л.В. Иммунные факторы в этиологии и патогенезе осложнений беременности. Акушерство и гинекология. 2012; 1: 128-36. [Sukhikh G.T., Vanko L.V. Immune factors in the etiology and pathogenesis of pregnancy complications. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2012; (1): 128-36. (in Russian)]
  19. Сидо£ова И.С., Никитина Н.А. Особенности патогенеза эндотелиоза при преэклампсии. Акушерство и гинекология. 2015; 1: 72-8. [Sidorova I.S., Nikitina N.A. Pathogenesis of endotheliosis in preeclampsia. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2015; (1): 72-8. (in Russian)]
  20. Кузник Б.И., Васильев В.Н., Цыбиков Н.Н. Иммуногенез, гемостаз и неспецифическая резистентность организма. М.: Медицина; 1989. 320с. [Kuznik B.I. Vasiliev V.N., Tsybikov N.N. Immunogenesis, hemostasis, and non-specific resistance of the organism. Moscow: Meditsina; 1989. 320p. (in Russian)]
  21. Кузник Б.И. Клеточные и молекулярные механизмы регуляции системы гемостаза в норме и патологии. Чита: Экспресс-издательство; 2010. 828с. [Kuznik B.I. Cellular and molecular mechanisms of regulation of the hemostatic system in health and disease. Chita: Express Publishing; 2010. 828p. (in Russian)]
  22. Кузник Б.И. Цитокины и система гемостаза. III. Цитокины и фибринолиз. Тромбоз, гемостаз и реология. 2012; 4: 17-27. [Kuznik B.I. Cytokines and hemostasis system. III. Cytokines and fibrinolysis. Tromboz, gemostaz i reologiya. 2012; 4: 17-27. (in Russian)]
  23. Lash G.E., Otun H.A., Innes B.A., Bulmer J.N., Searle R.F., Robson S.C. Low oxygen concentrations inhibit trophoblast cell invasion from early gestation placental explants via alterations in levels of the urokinase plasminogen activator system. Biol. Reprod. 2006; 74(2): 403-9.
  24. Hossain N., Schatz F., Paidas M.J. Heparin and maternal fetal interface: why should it work to prevent pregnancy complications? Thromb. Res. 2009; 124(6): 653-5.
  25. Александрова Н.В., Баев О.Р. Ранние этапы становления системы мать-плацента-плод. Акушерство и гинекология. 2011; 8: 4-10. [Aleksandrova N.V., Bayev O.R. Early stages of formation of the mother-placenta-fetus system. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2011; (8): 4-10. (in Russian)]
  26. Момот А.П., Тараненко И.А., Цывкина Л.П., Фадеева Н.И., Сердюк Г.В., Кудинова И.Ю., Медведева М.В. Фибринолитическая активность крови на разных сроках физиологически протекающей беременности. Медицинский алфавит. 2014; 2(12): 20-5. [Momot A.P., Taranenko I.A., Tsyivkina L.P., Fadeeva N.I., Serdyuk G.V., Kudinova I.Yu., Medvedeva M.V. The fibrinolytic activity of the blood at different stages of physiological pregnancy. Meditsinskiy alfavit. 2014; 2(12): 20-5. (in Russian)]
  27. Момот А.П., Молчанова И.В., Батрак Т.А., Белозеров Д.Е., Трухина Д.А., Кудинова И.Ю., Максимова Н.В., Фадеева Н.И., Сердюк Г.В., Романов В.В. Референтные значения показателей системы гемостаза при физиологически протекающей беременности и после родоразрешения. Проблемы репродукции. 2015; 21(1): 89-97. [Momot A.P., Molchanova I.V., Batrak T.A., Belozerov D.E., Truhina D.A., Kudinova I.Yu., Maksimova N.V., Fadeeva N.I., Serdyuk G.V., Romanov V.V. The reference values of hemostasis system during physiological pregnancy and after delivery. Problemy reproduktsii. 2015; 21(1): 89-97. (in Russian)]
  28. Ба£каган З.С., Момот А.П. Диагностика и контролируемая терапия нарушений гемостаза. 3-е изд. М.: Ньюдиамед; 2008. 292с. [Barkagan Z.S., Momot A.P. Diagnosis and therapy controlled hemostasis disorders. 3rd ed. Moscow: Nyudiamed; 2008 292p. (in Russian)]
  29. Тет£уашвили Н.К., Агаджанова А.А. Программа обследования и предгеста-ционной подготовки пациенток с привычным выкидышем (клиническая лекция). Акушерство и гинекология. 2012; 6: 87-91. [Tetruashvili N.K., Agadzhanova A.A. An examination and pregestational preparation program for patients with recurrent miscarriage. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2012; (6): 87-91. (in Russian)]

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2017 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies