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Influence of single nucleotide polymorphisms of innate immunity and inflammatory response genes on humoral and cellular immune parameters in umbilical cord blood of newborns

https://doi.org/10.36604/1998-5029-2026-100-121-128

Abstract

Introduction. The development of the immune system of the fetus and newborn is a complex, multifactorial process in which heredity plays a key role.

Aim. To study the influence of single nucleotide polymorphisms (SNPs) in genes of innate immunity and inflammatory response on humoral and cellular parameters of umbilical cord blood of newborns.

Materials and methods. The study sample consisted of venous umbilical cord blood from 80 infants born at 38-40 weeks of gestation. Total immunoglobulin (Ig) G, M, and A concentrations in plasma were determined using enzyme-linked immunosorbent assay. Lymphocyte subpopulation composition was assessed using flow cytometry. SNP analysis of target genes was determined using polymerase chain reaction (PCR) with high-resolution melting (HRM) analysis or linear-after-the-exponential PCR (LATE-PCR) with fluorescent probes.

Results. Carriage of the G allele of IL6 rs2069837 SNP is associated with a lower concentration of total IgG (β = -1.81, p = 0.03). The minor G allele of TLR4 rs4986790 is associated with an increased level of total IgM in cord blood (β = 0.36, p = 0.04). The C allele of IL10 rs3024498 SNP is associated with an increase in the proportion of total T-lymphocytes (p = 0.006) and T-helpers (p = 0.04) along with a decreased content of NK cells (p = 0.02) in the umbilical cord blood of newborns.

Conclusions. The obtained data indicate the possible contribution of some SNPs of the IL6, TLR4 and IL10 genes to changes in humoral and cellular parameters of the umbilical cord blood of newborns, which justifies the need for further research aimed at confirming the identified associations and developing prognostic models for assessing the immune status of children at risk.

About the Authors

O. O. Nekrasova
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation

Olesya O. Nekrasova, PhD (Med.), Senior Staff Scientist, Laboratory of Mechanisms of Virus-Associated Developmental Pathologies

22 Kalinina Str., Blagoveshchensk, 675000 



D. A. Gassan
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation

Dina A. Gassan, PhD (Med.), Head of Laboratory, Laboratory of Mechanisms of Virus-Associated Developmental Pathologies

22 Kalinina Str., Blagoveshchensk, 675000 



References

1. Palmeira P., Quinello C., Silveira-Lessa A.L., Zago C.A., Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin. Dev. Immunol. 2012; 2012:985646. https://doi.org/10.1155/2012/985646

2. Fouda G.G., Martinez D.R., Swamy G.K., Permar S.R. The impact of IgG transplacental transfer on early life immunity. ImmunoHorizons 2018; 2(1):14–25. https://doi.org/10.4049/immunohorizons.1700057

3. Remizova I.I., Chistyakova G.N., Gazieva I.A., Lyapunov V.A., Ustyantseva L.S. [Immunological parametrs of umbilical cord blood from children born to women with urogenital infections]. Meditsinckaya immunologiya = Medical Immunology 2015; 17(3):253–260 (in Russian). https://doi.org/10.15789/1563-0625-2015-3-253-260

4. Gashimova N.R., Pankratyeva L.L., Bitsadze V.O., Khizroeva D.Kh., Makatsariya N.A., Tretyakova M.V., Shkoda A.S., Grigorieva K.N., Tsibizova V.I., Gris J.-C., Yakubova F.E., Blinov D.V., Makatsariya A.D. [Intrauterine activation of the fetal immune system in response to maternal COVID-19]. Akusherstvo, ginekologiya i reproduktsiya = Obstetrics, Gynecology and Reproduction 2023; 17(2):188–201 (in Russian). https://doi.org/10.17749/2313-7347/ob.gyn.rep.2023.404

5. Takeda K., Akira S. Toll-like receptors in innate immunity. Int. Immunol. 2005; 17(1):1–14. https://doi.org/10.1093/intimm/dxh186

6. Turner M.W. The role of mannose-binding lectin in health and disease. Mol. Immunol. 2003; 40(7):423–429. https://doi.org/10.1016/s0161-5890(03)00155-x

7. Kilpatrick D.C. Mannan-binding lectin: clinical significance and applications. Biochim. Biophys. Acta 2002; 1572(2- 3):401–413. https://doi.org/10.1016/s0304-4165(02)00321-5

8. Yan L., Cui Y., Feng J. Biology of pellino1: a potential therapeutic target for inflammation in diseases and cancers. Front. Immunol. 2023; 14:1292022. https://doi.org/10.3389/fimmu.2023.1292022

9. Yockey L.J., Iwasaki A. Interferons and proinflammatory cytokines in pregnancy and fetal development. Immunity 2018; 49(3):397–412. https://doi.org/10.1016/j.immuni.2018.07.017

10. Smith A.J., Humphries S.E. Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine Growth Factor Rev. 2009; 20(1):43–59. https://doi.org/10.1016/j.cytogfr.2008.11.006

11. Kalia N., Sharma A., Kaur M., Kamboj S.S., Singh J. A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene. Springerplus 2016; 5(1):811. https://doi.org/10.1186/s40064-016-2543-4

12. Hawn T.R., Misch E.A., Dunstan S.J., Thwaites G.E., Lan N.T., Quy H.T., Chau T.T., Rodrigues S., Nachman A., Janer M., Hien T.T., Farrar J.J., Aderem A. A common human TLR1 polymorphism regulates the innate immune response to lipopeptides. Eur. J. Immunol. 2007; 37(8):2280–2289. https://doi.org/10.1002/eji.200737034

13. Nekrasova O.O., Gassan D.A., Konev A.V., Koneva K.A. [Development of PCR-based test systems for genotyping of single nucleotide polymorphisms in innate immunity and inflammatory response genes]. Bulleten' fiziologii i patologii dykhaniya = Bulletin Physiology and Pathology of Respiration 2025; 98:109–116 (in Russian). https://doi.org/10.36604/1998-5029-2025-98-109-116

14. Dienz O., Eaton S.M., Bond J.P., Neveu W., Moquin D., Noubade R., Briso E.M., Charland C., Leonard W.J., Ciliberto G., Teuscher C., Haynes L., Rincon M. The induction of antibody production by IL-6 is indirectly mediated by IL- 21 produced by CD4+ T cells. J. Exp. Med. 2009; 206(1):69–78. https://doi.org/10.1084/jem.20081571

15. Cerutti A. The regulation of IgA class switching. Nat. Rev. Immunol. 2008; 8(6):421–434. https://doi.org/10.1038/nri2322

16. Clements T., Rice T.F., Vamvakas G., Barnett S., Barnes M., Donaldson B., Jones C.E., Kampmann B., Holder B. Update on transplacental transfer of IgG subclasses: impact of maternal and fetal factors. Front. Immunol. 2020; 11:1920. https://doi.org/10.3389/fimmu.2020.01920

17. Borghi S., Bournazos S., Thulin N.K., Li C., Gajewski A., Sherwood R.W., Jagannathan P., Ravetch J.V., Wang T.T. FcRn, but not FcγRs, drives maternal-fetal transplacental transport of human IgG antibodies. Proc. Natl. Acad. Sci. USA 2020; 117(23):12943–12951. https://doi.org/10.1073/pnas.2004325117

18. Kong X., Sawalha A.H. Takayasu arteritis risk locus in IL6 represses the anti-inflammatory gene GPNMB through chromatin looping and recruiting MEF2-HDAC complex. Ann. Rheum. Dis. 2019; 78(10):1388–1397. https://doi.org/10.1136/annrheumdis-2019-215567

19. Gong B., Huang L., He Y., Xie W., Yin Y., Shi Y., Xiao J., Zhong L., Zhang Y., Jiang Z., Hao F., Zhou Y., Li H., Jiang L., Yang X., Song X., Kang Y., Tuo L., Huang Y., Shuai P., Liu Y., Zheng F. A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19. Signal Transduct. Target. Ther. 2022; 7(1):112. https://doi.org/10.1038/s41392-022-00923-1

20. Arbour N.C., Lorenz E., Schutte B.C., Zabner J., Kline J.N., Jones M., Frees K., Watt J.L., Schwartz D.A. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet. 2000; 25(2):187–191. https://doi.org/10.1038/76048

21. Saraiva M., O'Garra A. The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 2010; 10(3):170– 181. https://doi.org/10.1038/nri2711

22. Hutchins A.P., Diez D., Miranda-Saavedra D. The IL-10/STAT3-mediated anti-inflammatory response: recent developments and future challenges. Brief. Funct. Genomics 2013; 12(6):489–498. https://doi.org/10.1093/bfgp/elt028

23. Zhang G., Zhou B., Li S., Yue J., Yang H., Wen Y., Zhan S., Wang W., Liao M., Zhang M., Zeng G., Feng C.G., Sassetti C.M., Chen X. Allele-specific induction of IL-1β expression by C/EBPβ and PU.1 contributes to increased tuberculosis susceptibility. PLoS Pathogens 2014; 10(10):e1004426. https://doi.org/10.1371/journal.ppat.1004426


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Nekrasova O.O., Gassan D.A. Influence of single nucleotide polymorphisms of innate immunity and inflammatory response genes on humoral and cellular immune parameters in umbilical cord blood of newborns. Bulletin Physiology and Pathology of Respiration. 2026;(100):121-128. (In Russ.) https://doi.org/10.36604/1998-5029-2026-100-121-128

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ISSN 1998-5029 (Print)