IMMUNO-PHENOTYPIC PROPERTIES OF PERIPHERAL BLOOD LYMPHOCYTES OF INFERTILITY MEN WITH COMORBIDITIES

Authors

  • O. V. Melnyk DANYLO HALYTSKY LVIV NATIONAL MEDICAL UNIVERSITY
  • M. Z. Vorobets DANYLO HALYTSKY LVIV NATIONAL MEDICAL UNIVERSITY
  • R. V. Fafula DANYLO HALYTSKY LVIV NATIONAL MEDICAL UNIVERSITY
  • Z. D. Vorobets DANYLO HALYTSKY LVIV NATIONAL MEDICAL UNIVERSITY

DOI:

https://doi.org/10.11603/mcch.2410-681X.2022.i2.13088

Keywords:

infertility, idiopathic infertility, rheumatoid arthritis, blood serum, population composition of lymphocytes

Abstract

Introduction. It is known that approximately 15 % of married couples suffer from infertility, with the malefactor accounting for almost 50 % of cases. According to the traditional method of evaluation, in 30 % of patients, the etiology of the male contribution to infertility remains unexplained and, thus, is identified as idiopathic. Therefore, the diagnosis of male infertility cannot be limited only a simple sperm analysis. The regulation of male reproductive function is multi-level, involving not only the endocrine system, but also the immune system. Male infertility is also observed with other accompanying pathologies, in particular, rheumatoid arthritis. For a better understanding of the immunopathogenic mechanisms of infertility, it is necessary to study the role of various immune factors.

The aim of the study – to evaluate the population composition and activation markers of peripheral blood lymphocytes of men with idiopathic infertility and autoimmune joint pathology.

Research Methods. The research was carried out on blood serum and seminal plasma of 45 infertile men aged 22–48: with idiopathic infertility (n=23) and autoimmune joint pathology – rheumatoid arthritis (n=22). 27 fertile healthy men of the same age were included in the control group. To determine the quantitative parameters of lymphocytes of the main populations and subpopulations in the blood of patients with idiopathic infertility and autoimmune pathology of the joints, the method of flow cytometry with monoclonal antibodies labeled with fluorescein (BD Biosciences, USA) was used. The number of lymphocytes was determined on a flow cytometer BD FacsCalibur (Becton Dickinson, USA).

Results and Discussion. It was shown that the number of lymphocytes of subpopulations practically did not differ in infertile men from similar indicators of the control group in terms of absolute values. However, it was found that in men with idiopathic infertility, there is a probable increase in the content of CD4+CD25+ T-lymphocytes in the blood, from (0.357±0.185) to (0.504±0.220) G/l (р<0.05). No significant changes were found in autoimmune pathology. Infertile men with autoimmune pathology are distinguished from controls by increased numbers of CD8+ cells and activated T-lymphocytes. The most deviations from control were registered in persons with idiopathic infertility: a reduced number of naive CD4+CD25 lymphocytes with a simultaneous increase in the number of CD4+CD25+ regulatory T-cells, which indicates the conversion of naive T-lymphocytes into regulatory cells.

Conclusions. It was found that the development of infertility against the background of various accompanying pathologies is accompanied by changes in indicators of both systemic and local immune reactivity. The nature of these changes differs depending on the accompanying pathology. The study of the characteristic signs of immune reactivity disorders in infertile men with comorbidities make it possible to position some of them as reliable markers for predicting reproductive function disorders.

References

Tahmasbpour, E., Balasubramanian, D, Agarwal, A. (2014). A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART). J. Assist. Reprod. Genet., 31, 1115-1137. DOI 10.1007/s10815-014-0280-6.

Zargar, M.H., Ahmad, F., Lateef, M., Malla, T.M. (2021). Understanding male infertility for promising ART. Infertility and Assisted Reproduction, 141. DOI: 10.5772/intechopen.98504.

Baczkowski, T., & Kurfzawa, R. (2007). Immunophenotypic profiles of peripheral blood lymphocytes on the day of embryo transfer in women undergoing in vitro fertilization. Folia Histohemica et Cytobiologica, 45 (1), 73-77.

Bhushan, S., Theas, M.S., Guazzone, V.A., ­Jacob, O.P., Wang, M., Fijak, M., et al. (2020). Immune cell subtypes and their function in the testis. Front Immunol., 11, 583304. DOI: 10.3389/fimmu.2020.583304.

Gong, J., Zeng, Q., Yu, D., Yong-Gang Duan, Y.-G. (2020). T Lymphocytes and testicular immunity: A new insight into immune regulation in testes. Int. J. Mol. Sci., 22 (1), 57. DOI: 10.3390/ijms22010057.

Jafarpour, R., Pashangzadeh, S., Mehdizadeh, S., Hashem Bayatipoor, H., Shojaei, Z., Motallebnezhad, M. (2020). Functional significance of lymphocytes in pregnancy and lymphocyte immunotherapy in infertility: A comprehensive review and update. Int Immuno­pharmacol., 87, 106776. DOI: 10.1016/j.intimp.2020. 106776.

Krivonos, M., Khiozroeva, J.Kh., Zainulina, M.S. et al. (2022). The role of lymphocytic cells in infertility and reproductive failures in women with antiphospholipid antibodies. J. Matertn Fetal Neonatal Med., 35 (5), 871-877. DOI: 10.1080/14767058.2020.1732343.

Kaur, G., Thompson, L.A., Dufour, J.M. (2014). Sertoli cells-immunological sentinels of spermatogenesis. Semin. Cell Dev. Biol., 0, 36-44. DOI: 10.1016/j.semcdb. 2014.02.011.

Cheng, C.Y., Mruk, D.D. (2012). The blood-testis barrier and its implications for male contraception. Pharmacol. Rev., 64 (1), 16-64.

Jacobo, P., Perez, C., Theas, M.S. (2011). CD4+ and CD8+ cells producing Th1 and Th17 cytokines are involved in the pathogenesis of autoimmune orchitis. Reproduction, 141, 259-268.

Bo, M., Jasemi, S., Uras, G. (2020). Role of Infections in the pathogenesis of rheumatoid arthritis: Focus on mycobacteria. Microorganisms, 8 (10), 1459, 1-19. https://doi.org/10.3390/microorganisms8101459.

Fattah, A., Asadi, A., Shayesteh, M.R.H., He­sa­ri, F.H., Jamalzehi, S., Abbasi, M., et al. (2020). Fertility and infertility implications in rheumatoid arthritis; state of the art. Inflamm. Res., 69 (8), 721-729. DOI: 10.1007/s00011-020-01362-w.

Kosmaczewska, A., Swierkot, J., Ciszak, L., et al. (2013). Alterations in both the activatory and inhibitory potential of peripheral blood CD4+ T Cells un rheumatoid arthritis patients correlate with disease progression. Pathol. Oncol. Res., 9. DOI 10.1007/s12253-013-9687-0.

Ling, E., Shubinsky, G., Press, J. (2007). Increasd proportion of CD3+CD4-CD8- double-negative T-cells in peripheral blood of children with Bahcet's disease. Autoimmunity Reviews, 6, 237-240.

Pierucci-Alves, F., Yi, S., Schultz, B.D. (2012). Transforming factor beta 1 induces tight junction disruption and loss of transepithelial resistance across porcine vas deferens epitthelial cells. Biology of Reproduction, 86 (2), 1-8.

McInnes, I.B., Schett, G. (2007). Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol., 7, 429-442. DOI: 10.1038/nri2094.

Brennan, F.M., McInnes, I.B. (2008). Evidence that cytokines play a role in rheumatoid arthritis. J. Clin. Investig., 118, 3537-3545. DOI: 10.1172/JCI36389.

Coutant, F., Miossec, P. (2020). Evolving concepts of the pathogenesis of rheumatoid arthritis with focus on the early and late stages. Curr. Opin. Rheuma­tol., 32, 57-63. DOI: 10.1097/BOR.0000000000000664.

Zhao, Z., He, S., Tang, S. (2022). CLP1 is a prognosis-related biomarker and correlates with immune infiltrates in rheumatoid arthritis. Front Pharmacol.,13, 827215. DOI: 10.3389/fphar.2022.827215.

Alivernini, S., Tolusso, B., Petricca, L., Ferraccioli, G., Gremese, E. (2019). Mosaic of autoimmu­nity. Elsevier; Amsterdam, The Netherlands: Chapter 16. Rheumatoid arthritis.

Klareskog, L., Catrina, A.I., Paget, S. (2009). Rheumatoid arthritis. Lancet, 373, 659-672. DOI: 10.1016/S0140-6736(09)60008-8.

McInnes, I.B., & Schett, G. (2011). The pathogenesis of rheumatoid arthritis. N Eng J Med., 365, 2205-2219. DOI: 10.1056/NEJMra1004965.

Doorenspleet, M.E., Klarenbeek, P.L., de Hair, M.J., van Schaik, B.D., Esveldt, R.E., van Kampen, A.H., Gerlag, D.M., Musters, A., Baas, F., Tak, P.P., et al. (2014). Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with auto­reactivity. Ann Rheum Dis., 73, 756-762. DOI: 10.1136/annrheumdis-2012-202861.

Gaffen, S.L., Jain, R., Garg, A.V., Cua, D.J. (2014). The IL-23-IL-17 immune axis: From mechanisms to therapeutic testing. Nat Rev Immunol., 14, 585-600. DOI: 10.1038/nri3707.

Lubberts, E. (2015). The IL-23-IL-17 axis in inflammatory arthritis. Nat. Rev. Rheumatol., 11, 415-429. DOI: 10.1038/nrrheum.2015.53.

Hussein, H.M., & Rahal, E.A. (2019). The role of viral infections in the development of autoimmune diseases. Crit. Rev. Microbiol., 45, 394-412. DOI: 10.1080/1040841X.2019.1614904.

Listing, J., Gerhold, K., Zink, A. (2012). The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology, 52, 53-61. DOI: 10.1093/rheumatology/kes305.

Venigalla, S.S.K., Premakumar, S., Janakiraman, V. (2020). A possible role for autoimmunity through molecular mimicry in alphavirus mediated arthritis. Sci. Rep., 10, 938. DOI: 10.1038/s41598-019-55730-6.

Published

2022-10-04

How to Cite

Melnyk, O. V., Vorobets, M. Z., Fafula, R. V., & Vorobets, Z. D. (2022). IMMUNO-PHENOTYPIC PROPERTIES OF PERIPHERAL BLOOD LYMPHOCYTES OF INFERTILITY MEN WITH COMORBIDITIES. Medical and Clinical Chemistry, (2), 5–12. https://doi.org/10.11603/mcch.2410-681X.2022.i2.13088

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Section

ORIGINAL INVESTIGATIONS