Regulation of the functional activity of peripheral B lymphocytes in pregnant women with a history of recurrent miscarriage

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

BACKGROUND: The frequency of recurrent miscarriage is up to 5 % of all desired pregnancies and is mainly due to immunological disorders. Dysfunction in the regulation of the functional activity of B lymphocytes is the pathogenetic link in multiple obstetric complications, including habitual miscarriage.

AIM: The aim of this study was to characterize the regulation of the functional activity of peripheral B lymphocytes in pregnant women with threatened spontaneous miscarriage and a history of habitual miscarriage.

MATERIALS AND METHODS: We examined 88 women aged 18-40 years at a gestation period of 5-12 weeks. The main group consisted of 36 patients with threatened spontaneous miscarriage at the time of examination and a history of habitual miscarriage. The control group included 28 women with uncomplicated pregnancy. The comparison group consisted of 24 primary pregnant patients with threatened spontaneous abortion at the time of examination. BAFF and APRIL levels in the blood serum were determined by enzyme immunoassay. The content of CD19+BAFFR+ B lymphocytes in the lymphocyte gate was evaluated in the peripheral blood by flow cytometry using monoclonal antibodies. Akt mRNA expression was assessed using real-time reverse-transcription quantitative polymerase chain reaction. CD19+ В lymphocytes were isolated by direct magnetic separation.

RESULTS: In the main group, there was an increase in expression of BAFF receptors on peripheral CD19+ B lymphocytes and a decrease in the serum BAFF concentration compared to the parameters in the other study groups. We also found a pronounced trend towards a decrease in the serum APRIL level in the main and comparison groups of patients compared to healthy pregnant women. Besides, Akt mRNA expression in peripheral CD19+ B lymphocytes was increased in the main group.

CONCLUSIONS: Threatened habitual abortion is associated with the deficit of the regulatory influence of BAFF and APRIL, which is expressed in the disruption of B cell homeostasis and the weakening of humoral effector mechanisms.

About the authors

Anna I. Malyshkina

Ivanovo Research Institute of Maternity and Childhood named after V.N. Gorodkov

Email: anna_im@mail.ru
ORCID iD: 0000-0002-1145-0563

MD, Dr. Sci. (Med.), Professor

Russian Federation, 20 st. Victory, Ivanovo

Natalia Y. Sotnikova

Ivanovo Research Institute of Maternity and Childhood named after V.N. Gorodkov

Email: niimid.immune@mail.ru
ORCID iD: 0000-0002-0608-0692

MD, Dr. Sci. (Med.), Professor

Russian Federation, 20 st. Victory, Ivanovo

Dmitriy N. Voronin

Ivanovo Research Institute of Maternity and Childhood named after V.N. Gorodkov

Email: niimid.immune@mail.ru
ORCID iD: 0000-0003-2836-8694

Cand. Sci. (Biol.)

Russian Federation, 20 st. Victory, Ivanovo

Alena V. Kust

Ivanovo Research Institute of Maternity and Childhood named after V.N. Gorodkov

Author for correspondence.
Email: avkMD@yandex.ru
Russian Federation, 20 st. Victory, Ivanovo

References

  1. Komilzhanova DK. The role of antiphospholipid syndrome in the prevention of miscarriage. Biology and Integrative Medicine. 2017;(5):21–27. (In Russ.)
  2. Dobrokhotova YuE, Gankovskaya LV, Bakhareva IV, et al. Role of immune mechanisms in the pathogenesis of miscarriage. Obstetrics and Gynecology. 2016;(7):5–10. (In Russ.). doi: 10.18565/aig.2016.7.5-10
  3. Batrak NV, Malyshkina AI, Sotnikova NYU, et al. The role of cd178+ mononuclear cells in the development of threatened late abortion in women with first-trimester threatened pregnancy interruption and a history of recurrent miscarriage. Obstetrics and Gynecology. 2020;(5):70–77. (In Russ.). doi: 10.18565/aig.2020.5.70-77
  4. Lima J., Cambridge G., Vilas-Boas A. et al. Serum markers of B-cell activation in pregnancy during late gestation, delivery, and the postpartum period. Am J Reprod Immunol. 2019;81(3):e13090. doi: 10.1111/aji.13090
  5. Hu S, Wang R, Zhang M, et al. BAFF promotes T cell activation through the BAFF-BAFF-R-PI3K-Akt signaling pathway. Biomed Pharmacother. 2019;114:108796. doi: 10.1016/j.biopha.2019.108796
  6. Zheng N, Wang D, Ming H, et al. BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R. BMC Nephrol. 2015;16:72. doi: 10.1186/s12882-015-0064-y
  7. Samy E, Wax S, Huard B, et al. Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. Int Rev Immunol. 2017;36(1):3–19. doi: 10.1080/08830185.2016.1276903
  8. Matsuda Y, Haneda M, Kadomatsu K, Kobayashi T. A proliferation-inducing ligand sustains the proliferation of human naïve (CD27⁻) B cells and mediates their differentiation into long-lived plasma cells in vitro via transmembrane activator and calcium modulator and cyclophilin ligand interactor and B-cell mature antigen. Cell Immunol. 2015;295(2):127–136. doi: 10.1016/j.cellimm.2015.02.011
  9. Xu J, Luo X, Qu S, et al. B cell activation factor (BAFF) induces inflammation in the human fallopian tube leading to tubal pregnancy. BMC Pregnancy Childbirth. 2019;19(1):169. doi: 10.1186/s12884-019-2324-5
  10. Guo WJ, Qu X, Yang MX, et al. Expression of BAFF in the trophoblast and decidua of normal early pregnant women and patients with recurrent spontaneous miscarriage. Chin Med J (Engl). 2008;121(4):309–315.
  11. Frolova MV. The character of baff production and reception during pregnancy complicated intrauterine growth retardation. Russian journal of immunology. 2016;19(2(1):215–216. (In Russ.)
  12. Danaii S, Ghorbani F, Ahmadi M, et al. IL-10-producing B cells play important role in the pathogenesis of recurrent pregnancy loss. Int Immunopharmacol. 2020;87:106806. doi: 10.1016/j.intimp.2020.106806
  13. Chan CT, Lieu M, Sobey CG, et al. Diagnosing and treating hypertensive disorders of pregnancy? The answer may now be less BAFF-ling. Hypertension. 2017;70(5):884–886. doi: 10.1161/HYPERTENSIONAHA.117.09849
  14. Jiang N, Dai Q, Su X, et al. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior. Mol Biol Rep. 2020;47(6):4587–4629. doi: 10.1007/s11033-020-05435-1
  15. Ogunleye O, Campo B, Herrera D, et al. Relaxin confers cytotrophoblast protection from hypoxia-reoxygenation injury through the phosphatidylinositol 3-kinase-Akt/protein kinase B cell survival pathway. Am J Physiol Regul Integr Comp Physiol. 2017;312(4):R559–R568. doi: 10.1152/ajpregu.00306.2016
  16. Lima J, Cambridge G, Vilas-Boas A, et al. Serum markers of B-cell activation in pregnancy during late gestation, delivery, and the postpartum period. Am J Reprod Immunol. 2019;81(3):e13090. doi: 10.1111/aji.13090

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2021 Eсо-Vector



This website uses cookies

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

About Cookies