Isolation of donor gamma globulin obtained from multiparous women and its effects upon expression of HLA-G and HLA-DR molecules on lymphocytes from mothers of children with septal congenital heart defects
- 作者: Shabaldin A.1, Sinitskaya A.1, Shmulevich S.1, Grishacheva E.1, Shabaldina E.2, Deeva N.1
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隶属关系:
- Research Institute for Complex Issues of Cardiovascular Diseases
- Kemerovo State Medical University
- 期: 卷 27, 编号 1 (2024)
- 页面: 71-84
- 栏目: ORIGINAL ARTICLES
- URL: https://journals.rcsi.science/1028-7221/article/view/263665
- DOI: https://doi.org/10.46235/1028-7221-14186-IOD
- ID: 263665
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A common pathogenetic mechanism of reproductive losses and congenital heart disease (CHD) is associated with immune inflammation in the “mother-embryo” system which affects differentiation and proliferation of cardiovascular progenitor cells. It is hypothesized that this link may be blocked by regulatory auto- and alloimmune antibodies to HLA-G and HLA-DR molecules. Moreover, these antibodies may be present at sufficient amounts in donor immunoglobulins, especially those obtained from the blood of multiparous women. Based on this suggestion, the aim of our study was to obtain enriched gamma globulin fraction from the blood of multiparous women and evaluate its functional effects towards HLA-DR and HLA-G molecules.
Isolation of the gammaglobulin fraction (GGF) from the blood plasma of multiparous women was performed using affinity chromatography in several sessions. Purity grade of the resulting protein was analyzed by immunoelectrophoresis, electrophoretic separation of the protein fraction of blood serum and electrophoresis in 4.12% polyacrylamide gel with the addition of SDS (PAGE electrophoresis). PAAG electrophoresis showed that this GGF did not differ from commercial therapeutic intravenous immunoglobulin (IVIG).
Assessment of the functional activity of GGF upon HLA-DR and HLA-G molecules was performed in the main group of women and their children with congenital heart disease (n = 38), and control group of women who gave birth to conditionally healthy children (n = 21). To determine the specificity of GGF with respect to HLA-G, HLA-DR molecules, as well as to compare its effect with autologous and allogeneic sera and IVIG, we developed an immunological testing protocol using flow cytometry. The protocol was arranged on the basis of the methodology of “cross-match” approach and Russian patent “Method for determining antibodies to HLA-G”. It was found that the blocking activity of female serum towards autologous (intrinsic) and allogeneic (embryo/fetus/child) HLA-G and HLA-DR molecules may determine the protective effect on development of congenital heart defects in the next generation. Donor human immunoglobulin showed a similar blocking effects to these molecules, possibly due to the presence of alloimmune antibodies to HLA classes I and II. The gammaglobulin fraction obtained from the donor blood of multiparous women has a more pronounced blocking effect on the HLA-G and HLA-DR expression. Hence, this immunobiological preparation can be considered a prototype of therapeutic and prophylactic agent blocking the genesis of congenital heart defects.
作者简介
A. Shabaldin
Research Institute for Complex Issues of Cardiovascular Diseases
Email: cepoav1991@gmail.com
ORCID iD: 0000-0002-8785-7896
PhD, MD (Medicine), Associate Professor, Leading Research Associate, Laboratory of Heart Diseases
俄罗斯联邦, 6 Sosnoviy Blvd, Kemerovo, 650002Anna Sinitskaya
Research Institute for Complex Issues of Cardiovascular Diseases
编辑信件的主要联系方式.
Email: cepoav1991@gmail.com
ORCID iD: 0000-0002-4467-8732
PhD (Biology), Research Associate, Laboratory of Genomic Medicine
俄罗斯联邦, 6 Sosnoviy Blvd, Kemerovo, 650002S. Shmulevich
Research Institute for Complex Issues of Cardiovascular Diseases
Email: cepoav1991@gmail.com
ORCID iD: 0000-0002-7316-2962
PhD (Medicine), Pediatric Cardiologist
俄罗斯联邦, 6 Sosnoviy Blvd, Kemerovo, 650002E. Grishacheva
Research Institute for Complex Issues of Cardiovascular Diseases
Email: cepoav1991@gmail.com
Clinical Resident
俄罗斯联邦, 6 Sosnoviy Blvd, Kemerovo, 650002E. Shabaldina
Kemerovo State Medical University
Email: cepoav1991@gmail.com
ORCID iD: 0000-0002-0450-2767
PhD, MD (Medicine), Head, Department of Otorhinolaryngology
俄罗斯联邦, KemerovoN. Deeva
Research Institute for Complex Issues of Cardiovascular Diseases
Email: cepoav1991@gmail.com
ORCID iD: 0000-0002-6162-4808
Cardiologist
俄罗斯联邦, 6 Sosnoviy Blvd, Kemerovo, 650002参考
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