Comparison of serum levels of interleukin 33 in combination with serum levels of C-reactive protein, Immunoglobulin G, Immunoglobulin A, and Immunoglobulin M in recurrent pregnancy loss: A case-control study

Abstract

Background: One of the critical cases of recurrent pregnancy loss is immunological factors, whereas obtaining effective prevention or treatment is necessary for cognition of reasons. Objective: In this study, we tried to evaluate some immunological factors related to recurrent pregnancy loss.


Materials and Methods: This case-control study was conducted on 66 women at the age of 18–35 yr who were referred to the Clinic of Gynecology and Obstetrics, Ali Ibn Abi Taleb hospital, Zahedan, Iran, from August-December 2019. Interleukin 33 (IL-33) serum levels were measured using enzyme-linked immunosorbent assay. Immunoglobulin G, Immunoglobulin A, Immunoglobulin M (IgM), and C-reactive protein levels were measured by serology and hematology methods.


Results: The mean age of total participants was 30.8 ± 3.80 yr. The mean serum IL-33 in the case group was 318.5± 254.1 pg/ml and was lower than the control group (354.2± 259.9 pg/ml), which was not statistically significant (p = 0.52). The level of C-reactive protein in the case and control was not significantly different (p = 0.27), and Immunoglobulin A and Immunoglobulin G in the case and control were also not significantly different) p = 0.46, and p = 0.16, respectively), but there were significant differences (p= 0.003) between the level of the IgM in the case and control groups.


Conclusion: No statistically significant difference was observed in the IL-33 serum level, for at least 4–6 months after the last abortion in the case group and the final live birth in the control group. In contrast, serum levels of IgM were statistically significant. Finally, the need for more studies is felt according to the different results of the previous studies in this field.


Key words: Interleukin-33, Abortion, IgG, IgA, IgM.

References
[1] ESHRE Guideline Group on RPL, Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, et al. ESHRE guideline: Recurrent pregnancy loss. Hum Reprod Open 2018; 2018: hoy004.

[2] Yalcintepe SA, Silan F, Hacivelioglu SO, Uludag A, Cosar E, Ozdemir O. Fetal VEGF genotype is more important for abortion risk than mother genotype. Int J Mol Cell Med 2014; 3: 88–94.

[3] Deshmukh H, Way SS. Immunological basis for recurrent fetal loss and pregnancy complications. Annu Rev Pathol 2019; 14: 185–210.

[4] Elkarhat Z, Kindil Z, Zarouf L, Razoki L, Aboulfaraj J, Elbakay C, et al. Chromosomal abnormalities in couples with recurrent spontaneous miscarriage: A 21-year retrospective study, a report of a novel insertion, and a literature review. J Assist Reprod Genet 2019; 36: 499– 507.

[5] Khamees DA, Al-Ouqaili MTS. Cross-sectional study of chromosomal aberrations and immunologic factors in Iraqi couples with recurrent pregnancy loss. PeerJ 2022; 10: e12801.

[6] Asgari A, Ghahremani S, Saeedi S, Kamrani E. The study of chromosomal abnormalities and heteromorphism in couples with 2 or 3 recurrent abortions in Shahid Beheshti Hospital of Hamedan. Iran J Reprod Med 2013; 11: 201– 208.

[7] Ticconi C, Pietropolli A, Di Simone N, Piccione E, Fazleabas A. Endometrial immune dysfunction in recurrent pregnancy loss. Int J Mol Sci 2019; 20: 5332.

[8] Chatterjee P, Chiasson VL, Bounds KR, Mitchell BM. Regulation of the anti-inflammatory cytokines interleukin-4 and interleukin-10 during pregnancy. Front Immunol 2014; 5: 253.

[9] Moghbeli M. Genetics of recurrent pregnancy loss among Iranian population. Mol Genet Genomic Med 2019; 7: e891.

[10] Kamrani A, Rahmani SA, Mosapour P, Chavoshi R. Association of IL-33 gene rs16924159 polymorphism and recurrent pregnancy loss in Iranian Azeri women. Horm Mol Biol Clin Investig 2020; 41: 20200010.

[11] Valero-Pacheco N, Tang EK, Massri N, Loia R, Chemerinski A, Wu T, et al. Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice. Proc Natl Acad Sci USA 2022; 119: e2123267119.

[12] Topping V, Romero R, Than NG, Tarca AL, Xu Z, Kim SY, et al. Interleukin-33 in the human placenta. J Matern Fetal Neonatal Med 2013; 26: 327–338.

[13] Soheilyfar S, Nikyar T, Fathi Maroufi N, Mohebi Chamkhorami F, Amini Z, Ahmadi M, et al. Association of IL-10, IL-18, and IL-33 genetic polymorphisms with recurrent pregnancy loss risk in Iranian women. Gynecol Endocrinol 2019; 35: 342–345.

[14] Yue J, Tong Y, Xie L, Ma T, Yang J. Genetic variant in IL- 33 is associated with idiopathic recurrent miscarriage in Chinese. Sci Rep 2016; 6: 23806.

[15] Larsen EC, Christiansen OB, Kolte AM, Macklon N. New insights into mechanisms behind miscarriage. BMC Med 2013; 11: 154.

[16] Kaitu’u-Lino TJ, Tuohey L, Tong S. Maternal serum interleukin-33 and soluble ST2 across early pregnancy, and their association with miscarriage. J Reprod Immunol 2012; 95: 46–49.