Altered expression of cell membrane HLA-G molecules in mothers of children with inborn heart defects upon exposure to plasma gamma-globulin from multiparous women

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Abstract

High incidence of newborns with inborn heart defects (HD) and sufficient contribution of this disorder into perinatal, infant and pediatric mortality, as well as disability levels, even after radical surgical treatment determine significance of search for novel methods of prediction and prevention of appropriate HD risks at the stage of pregnancy planning. HLA-G is among key molecules participating in immune interactions between maternal microenvironment and embryos. Maximal antibody titers for HLA antigens is detected in multiparous women. However, the question remains open, which HLA molecules participate in blockage of immune inflammation in the mother-embryo system: either by maternal antibodies, or by donor immune globulins. Hence, the aim of our study was to obtain enriched γ-globulin preparation from blood of multiparous women and evaluation of its activity towards female HLA-G molecules. The γ-globulin fraction (GGF) was obtained from blood plasma of muliparous women by means of affine chromatography using DEAE Affi-Gel Blue system (BioRad, USA). We have formed 2 groups: a control group (14 healthy males), and experimental group of 14 women who gave birth to the children with inborn heart defects.
The changes of HLA-G expression on lymphocytes exposed to GGF were evaluated according to a flow cytometry protocol with calculation of percentage values using appropriate quotients. Evaluation of functional activity exerted by the GGF concentrate in control group showed inhibition of HLA-G expression on CD3+ and CD--lymphocytes against effects of autologous serum. GGF effects in experimental group upon HLA-G expression were differently directed, e.g., GGF sufficiently inhibited membrane HLA-G expression on the CD3-negative lymphocytes, compared to control group. Meanwhile, GGF showed stimulatory effect upon CD3+-lymphocytes, or it did not show any inhibitory action. The preparation obtained may serve as prototype for intravenous infusion. Moreover, in future one may use such immunoglobulin preparations, both for immune prophylaxis of non-syndromal sporadic HDs at the pregragravidary stage, as well as at early terms of pregnancy. The therapeutic effect will achieved due to blockage of embryoblast HLA molecules available to recognition. 

About the authors

A. V. Shabaldin

Research Institute for Complex Issues of Cardiovascular Diseases; Kemerovo State Medical University

Author for correspondence.
Email: weit2007@yandex.ru
ORCID iD: 0000-0002-8785-7896

PhD, MD (Medicine), Associate Professor, Leading Research Associate, Laboratory of Heart Defects; Professor, Department of Microbiology, Immunology
and Virology

650002, Kemerovo, Sosnoviy blvrd, 6

Russian Federation

N. S. Deeva

Research Institute for Complex Issues of Cardiovascular Diseases

Email: deevns@kemcardio.ru
ORCID iD: 0000-0002-6162-4808

Ordinator

650002, Kemerovo, Sosnoviy blvrd, 6

Russian Federation

А. S. Sukhikh

Kemerovo State Medical University

Email: suhih_as@list.ru
ORCID iD: 0000-0001-9300-5334

PhD, MD (Pharmacy), Senior Research Associate, Central Research Laboratory

Kemerovo

Russian Federation

G. V. Vavin

Kemerovo State Medical University

Email: okb-lab@yandex.ru
ORCID iD: 0000-0002-5171-8261

PhD (Medicine), Head, Central Research Laboratory

Kemerovo

Russian Federation

P. M. Kryukov

Kemerovo State Medical University

Email: weit2007@yandex.ru

PhD (Medicine)

Kemerovo

Russian Federation

References

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  2. Способ определения антител к аллогенным HLA-G. Шабалдин А.В., Мозес В.Г., Беленкова О.В., Шабалдина Е.В. Патент на изобретение RU 2585091 C1, 27.05.2016. Заявка № 2015101526/15 от 19.01.2015. [Method for the determination of antibodies to allogeneic HLA-G. Shabaldin A.V., Moses V.G., Belenkova O.V., Shabaldina E.V. Invention patent RU 2585091 C1, 05/27/2016. Application No. 2015101526/15 dated 19.01.2015].
  3. Шабалдин А.В., Шмулевич С.А., Чистякова Г.Н., Ремизова И.И., Лукоянычева Е.Б., Горшкова С.В., Шабалдина Е.В. Особенности аллогенных взаимодействий в краткосрочной культуре лимфоцитов супругов, имеющих детей с врожденными пороками сердца или ранние репродуктивные потери // Медицинская иммунология, 2019. Т. 21, № 2. С. 279-292. [Shabaldin A.V., Shmulevich S.A., Chistyakova G.N., Remizova I.I., Lukoyanycheva E.B., Gorshkova S.V., Shabaldina E.V. Peculiarities of allogenic interactions in the short-term culture of lymphocytes of spouses who have children with congenital heart diseases or early reproductive losses. Meditsinskaya immunologiya = Medical Immunology (Russia), 2019, Vol.21, no. 2, pp. 279-292. (In Russ.)] doi: 10.15789/1563-0625-2019-2-279-292.
  4. Wu Q.Y. To promote the sustainable development of surgical treatment for congenital heart disease by innovation and practice. Zhonghua Wai Ke Za Zhi, 2018, Vol. 56, no. 6, pp. 407-409.

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Copyright (c) 2021 Shabaldin A.V., Deeva N.S., Sukhikh А.S., Vavin G.V., Kryukov P.M.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
Свидетельство о регистрации СМИ ПИ № 77 - 11525 от 04.01.2002 выдано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).


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