The role of the HLA-complex genes in genesis of human idiopathic recurrent pregnancy loss

  • O. I. Terpyliak State Institution «Institute of Hereditary Pathology of the National, Academy of Medical Sciences of Ukraine», Ukraine, 79008, Lviv, M. Lysenko str., 31a https://orcid.org/0000-0001-6274-8362
  • D. V. Zastavna State Institution «Institute of Hereditary Pathology of the National, Academy of Medical Sciences of Ukraine», Ukraine, 79008, Lviv, M. Lysenko str., 31a https://orcid.org/0000-0002-3858-7180
  • K. O. Sosnina State Institution «Institute of Hereditary Pathology of the National, Academy of Medical Sciences of Ukraine», Ukraine, 79008, Lviv, M. Lysenko str., 31a https://orcid.org/0000-0003-4527-2010
  • O. L. Filenko Institute of Food Biotechnology and Genomics, NAS of Ukraine, Ukraine, 04123, Kyiv, Baidy-Vyshnevetskoho str., 2А https://orcid.org/0009-0002-7160-2546
DOI: https://doi.org/10.7124/FEEO.v33.1573
Keywords: idiopathic recurrent pregnancy loss, HLA genotyping

Abstract

Aim.To study the immunogenetic prerequisites of idiopathic recurrent spontaneous pregnancy losses in humans of allo- and autoimmune genesis. Methods. PCR-SSP (polymerase chain reaction with sequence-specific primers). Results. A comprehensive analysis of the distribution and frequency of allelic variants of the HLA-DRB1, HLA-DQA1, HLA-DQB1 genes testifies to an increased risk of recurrent pregnancy losses with a total homology of 50 % or more in couples and presence of the DQ2.5 genotype in a woman. The OR indicates that the risk of idiopathic recurrent spontaneous pregnancy loss increases 2.68 times when the homology of the couples is 50 % or more for two loci (HLA-DRB1, HLA-DQA1) and 12.8 times when the homology is 50 % or more for by three loci (HLA-DRB1, HLA-DQA1, HLA-DQB1), and if the DQ2.5 genotype is present in women, this risk increases 4 times. Conclusions. HLA genotyping of married couples with a history of spontaneous pregnancy loss is important for preconceptional prevention of recurrent pregnancy losses.

References

Królik M., Wrzesniak M., Jezela-Stanek A. Possible effect of the HLA-DQ2/DQ8 polymorphism on autoimmune parameters and lymphocyte subpopulation in recurrent pregnancy losses. J. Reprod. Immunol. 2022. Vol. 149. doi: 10.1016/j.jri.2021.103467.

Masucci L., D'Ippolito S., De Maio F., Quaranta G., Mazzarella R., Bianco D. M., Castellani R. et al. Celiak Disease Predisposition and Genital Tract Microbiota in Women Affected by Reccurent Pregnancy Loss. Nutrients. 2023. Vol. 15 (1). P. 221. doi: 10.3390/nu15010221.

Beydoun H., Saftlas A. F. Association of human leucocyte antigen sharing with recurrent spontaneous abortions. Tissue Antigens. 2005. Vol. 65(2). P. 123–135.

Varla-Leftherioti M., Keramitsoglou T., Spyropoulou-Vlachou M., Papadimitropoulos M., Kontopoulou-Antonopoulou V., Tsekoura C., Sankarkumar U. 14th International HLA and Immunogenetics Workshop: Report from the reproductive immunology component. Tissue Antigens. 2007. Vol. 69(1). Р. 297–303.

Dimitriadis E., Menkhorst E., Saito S., Kutteh W. H., Brosens J. J. Recurrent pregnancy loss. Nat. Rev. Dis. Primers. 2020. Vol. 10 (1). P. 98. doi: 10.1038/s41572-020-00228-z.

Egerup P., Kolte A. M., Larsen E. C., Krog M., Nielsen H. S., Christiansen O. B. Recurrent pregnancy loss: what is the impact of consecutive versus non-consecutive losses? Hum. Reprod. 2016. Vol. 31 (11). P. 2428–2434. doi: 10.1093/humrep/dew169.

Ober C. HLA and Pregnancy: The Paradox of the Fetal Allograft. Am J Hum Genet. 2002. Vol. 62 (1). P. 1–5. doi: 10.1086/301692.

Nakagawa K., Kuroda K., Sugiyama R., Yamaguchi K. After 12 consecutive miscarriages, a patient received immunosuppressive treatment and delivered an intact baby. Reprod. Med. Biol. 2017. Vol. 16 (3). P. 297–301. doi: 10.1002/rmb2.12040.

Sange I., Mohamed M. F., Aung S. et al. Celiac Disease and the Autoimmune Web of Endocrinopathies. Cureus. 2020. Vol. 12. doi: 10.7759/cureus.12383.

Vipin Gupta, Alka Singh, Rajesh Khadgawat, Ashish Agarwal, Asif Iqbal, Wajiha Mehtab, Chaturvedi P. K., Vineet Ahuja, Govind K Makharia The spectrum of clinical and subclinical endocrinopathies in treatment-naïve patients with celiac disease. Indian J. Gastroenterol. 2019. Vol. 38 (6). P. 518–526. doi: 10.1007/s12664-019-01006-w.

Grode L. B., Agerholm I. E., Humaidan P., Parkner T., Bech B. H., Ramlau-Hansen C. H., Jensen T. M. Unrecognised coeliac disease among men and women undergoing fertility treatment: A screening study. United European Gastroenterol. J. 2018. Vol. 6 (10). P. 1477–1484. doi: 10.1177/2050640618796750.

Caio G., Volta U., Sapone A., Leffler D., De Giorgio R., Catassi C., Fasano A. Celiac disease: a comprehensive current review. BMC Medicine. 2019. Vol. 17. P. 142. doi: 10.1186/s12916-019-1380-z.

Casella G., Orfanotti G., Giacomantonio L., Bella C. D., Crisafulli V., Villanacci V., Baldini V., Bassotti G. Celiac disease and obstetrical-gynecological contribution. Gastroenterol. Hepatol. Bed. Bench. 2016. Vol. 9 (4). P. 241–249.

Saccone G., Berghella V., Sarno L., Maruotti G.M., Cetin I., Greco L., Khashan A.S., McCarthy F., Martinelli D., Fortunato F., Martinelli P. Celiac disease and obstetric complications: A systematic review and metaanalysis. Am.. J Obstet. Gynecol. 2016. Vol. 214 (2) P. 225–234. doi: 10.1016/j.ajog.2015.09.080.

Makukh H. V., Zastavna D. V., Tyrkus M. J., Tretiak B. I., Chorna L. B. Sposib vydilennia DNK z leikocytiv peryferijnoi krovi: pat. 32044 Ukraina: MPK G01N33/49 (2006.01); No u200801896; appl. 14.02.2008; publ. 25.04.2008, bul. No. 8. [in Ukrainian]