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

Nikolaeva M.G., Serdyuk G.V., Gorbacheva T.I., Fadeeva N.I., Momot A.P.

1Altai State Medical University, Ministry of Health of Russia, Barnaul 656038, Lenina pr. 40, Russia 2Altai Branch, Hematology Research Center, Ministry of Health of Russia, Barnaul 656038, Lyapidevskogo str. 1, Russia
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 fibrinolysis 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.

Keywords

lymphocyte immunotherapy
fibrinolysis
tissue-type plasminogen activator 1
tissue-type plasminogen activator inhibitor-1
fibrin clot lysis time
tumor necrosis factor-α (TNF-α)
interleukin 10 (IL-10)

Supplementary Materials

  1. Figure 1. The level of TNF-α, IL-10 cytokines and TNF-α/IL-10 ratio in relation to LIT in comparison groups at 7-8 weeks (pg/ml) of gestation.
  2. Figure 2. Specific fibrinolytic reactions in relation to LIT in comparison groups at 7-8 weeks of gestation.
  3. Table. The level of plasminogen, D-dimers and time XIIa-ZF in relation to LIT in groups at 7-8 weeks of gestation.

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Received 25.10.2016

Accepted 11.11.2016

About the Authors

Nikolaeva Mariya Gennad’evna, candidate of medical Sciences, associate professor in the Obstetrics and Gynecology Department, Altai State Medical University,
Ministry of Health of Russia. 656038, Russia, Barnaul, Lenina pr. 40. E-mail: nikolmg@yandex.ru
Serdyuk Galina Valentinovna, MD, senior researcher of laboratory of hematology, Altai State Medical University, Ministry of Health of Russia.
656038, Russia, Barnaul, Lenina pr. 40. E-mail: Gvser@mail.ru
Gorbacheva Tatiana Ivanovna, candidate of medical sciences, associate professor in the Obstetrics and Gynecology Department, Altai State Medical University,
Ministry of Health of Russia. 656038, Russia, Barnaul, Lenina pr. 40. E-mail tg72@bk.ru
Fadeeva Natalya Ilyinichna, M. D., Professor, head of the department of obstetrics and gynecology, Altai State Medical University, Ministry of Health of Russia.
656038, Russia, Barnaul, Lenina pr. 40. E-mail: nat2fad@hotmail.com
Momot Andrey Pavlovich, MD, Professor, Director of Altai Branch, Hematology Research Center, Ministry of Health of Russia.
656038, Russia, Barnaul, Lyapidevskogo str. 1. E-mail: xyzam@yandex.ru

For citations: Nikolaeva M.G., Serdyuk G.V., Gorbacheva T.I., Fadeeva N.I., Momot A.P. Impact of lymphocyte therapy on blood fibrinolytic activity and immune responses in patients with a history of reproductive losses. Akusherstvo i Ginekologiya/
Obstetrics and Gynecology. 2017; (2): 24-30. (in Russian)
http://dx.doi.org/10.18565/aig.2017.2.24-30
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