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The function profile of γδТ-lymphocytes in patients with IgA-nephropathy

https://doi.org/10.28996/2618-9801-2022-1-72-81

Abstract

An actual challenge of current nephrology and immunology is the identification of new biomarkers that can be used as the potential key pathogenetic targets for monitoring, predicting, and effective treatment of IgA-nephropathy. The role of B-lymphocytes and αβТ-helpers in IgA-nephropathy immunopathogenesis is well studied. A promising direction is the investigation of mechanisms of non-classical γδТ-lymphocytes involvement, the effector role of which has been demonstrated in many autoimmune diseases. The aim of the work was to assess the phenotypic and functional characteristics of γδT-lymphocytes in the peripheral blood of patients with IgA-nephropathy. Materials and methods. The material of the study was the peripheral venous blood of 27 patients with IgA-nephropathy, which was confirmed by histological examination of biopsies using the Oxford classification (MEST-C). Phenotypic and functional markers of peripheral blood lymphoid cells were identified by the flow cytometry method. The data were processed using the Statistica 8.0 software. Results. The increase in the γδT-lymphocytes number (p<0.01) with a predominant cytotoxic CD8+CD56+CD314+ phenotype was established in association with the expansion of effector memory γδT-cells percentage (p<0.05) in peripheral blood of patients with IgA-nephropathy compared with healthy donors. The level of the killer receptor CD314 expression on γδT-cells correlated with the glomerular filtration rate under 60 ml/min (R= -0.62, p<0.01). It was shown that predominantly in patients with a high level of proteinuria (>500 mg/day) the number of effector memory γδT-cells exceeded their number in the group of patients with a low risk of progressive decline in renal function (p<0.05) and correlated with the severity of renal tissue morphological damage, in particular, mesangial proliferation (R=0.60; p<0.01) and segmental glomerulosclerosis (R=0.61; p<0.01). Conclusion. The functional profile of γδТ-lymphocytes can be used as a biomarker of the high risk of IgA-nephropathy progression as well as a therapeutic target for the subsequent development of specific immune-correction therapy.

About the Authors

D. . Nizheharodava
Belarusian Medical Academy of Post-Graduate Education; International Sakharov Environmental Institute, Belarusian State University
Russian Federation


K. . Komissarov
Belarusian Medical Academy of Post-Graduate Education; Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
Russian Federation


E. . Minchenko
1st City Clinical Hospital Minsk
Russian Federation


A. . Adamovich
Belarusian Medical Academy of Post-Graduate Education
Russian Federation


V. . Pilotovich
Belarusian Medical Academy of Post-Graduate Education
Russian Federation


M. . Zafranskaya
Belarusian Medical Academy of Post-Graduate Education; International Sakharov Environmental Institute, Belarusian State University
Russian Federation


References

1. Berger J., Hinglais N. Les dépôts intercapillaires d’IgA-IgG. J. Urol. Nephrol. 1968; 74: 694-695. PMID: 4180586.

2. Berger J. IgA glomerular deposits in renal disease. Transplant. Proc. 1969; 1: 939-944. PMID: 4107073.

3. Roberts I.S., Cook H.T., Troyanov S. et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009; 76: 546-556. doi: 10.1038/ki.2009.168.

4. Ruszkowski J., Lisowska K., Pindel M. T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target. Clin. Exp. Nephrol. 2019; 23: 291-303. doi: 10.1007/s10157-018-1665-0.

5. Barbour S.J., Espino-Hernandez G., Reich H.N. et al. The MEST score provides earlier risk prediction in lgA nephropathy. Kidney Int. 2016; 89: 167-75. doi: 10.1038/ki.2015.322.

6. Suzuki H., Kiryluk K., Novak J. et al. The pathophysiology of IgA nephropathy. J. Am. Soc. Nephrol. 2011; 22: 1795-803. doi: 10.1681/ASN.2011050464.

7. Kabelitz D. Gamma Delta T Cells (γδ T Cells) in Health and Disease: In Memory of Professor Wendy Havran. Cells. 2020; 9: 1-7. doi: 10.3390/cells9122564.

8. Chang S., Li X. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy. Front. Med. 2020; 7(92): 1-15. doi: 10.3389/fmed.2020.00092.

9. Peters C., Kabelitz D., Wesch D. Regulatory functions of γδ T cells. Cell. Mol. Life Sci. 2018; 75(12): 1-14. DOI: 10.1007/s00018-018-2788-x.

10. Paul S., Giri S., Lal G. Role of gamma-delta (γδ) T Cells in autoimmunity. J. Leukoc. Biol. 2015; 97: 259-271. doi: 10.1189/jlb.3RU0914-443R.

11. Fichtner A.S., Ravens S., Prinz I. Human γδ TCR Repertoires in Health and Disease. Cells. 2020; 9(800): 1-14. doi: 10.3390/cells9040800.

12. Yeo S.C., Cheung C.K., Barratt J. New insights into the pathogenesis of IgA nephropathy. Pediatr. Nephrol. 2018; 33: 763-777. doi: 10.1007/s00467-017-3699-z.

13. Wu H., Clarkson A.R., Knight J.F. Restricted γδ T-cell receptor repertoire in IgA nephropathy renal biopsies. Kidney Int. 2001; 60: 1324-31. doi: 10.1046/j.1523-1755.2001.00937.x.

14. Levey A.S., Stevens L.A., Schmid C.H. et al. Chronic Kidney Disease Epidemiology Collaboration. A New Equation to Estimate Glomerular Filtration Rate. Ann. Intern. Med. 2009; 150(5): 604-612. doi: 10.7326/0003-4819-150-9-200905050-00006.

15. Trimarchi H. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017; 91(5): 1014-1021. doi: 10.1016/j.kint.2017.02.003.

16. Suzuki H., Raska M., Yamada K. et al. Cytokines alter IgA1 O-glycosylation by dysregulating C1GalT1 and ST6GalNAc-II enzymes. J. Biol. Chem. 2014; 289: 5330-9. doi: 10.1074/jbc.M113.512277.

17. Lin J.-R., Wen J., Zhang H. et al. Interleukin-17 promotes the production of underglycosylated IgA1 in DAKIKI cells. Ren. Fail. 2018; 40: 60-7. doi: 10.1080/0886022X.2017.1419972.

18. Toyabe S., Harada W., Uchiyama M. Oligoclonally expanding gamma delta T lymphocytes induce IgA switching in IgA nephropathy. Clin. Exp. Immunol. 2001; 124: 110-7. doi: 10.1046/j.1365-2249.2001.01494.x.

19. Gibbings D., Befus A.D. CD4 and CD8: An inside-out coreceptor model for innate immune cells. J. Leukoc. Biol. 2009; 86: 251-259. doi: 10.1189/jlb.0109040.

20. Fonseca S., Pereira V., Lau C. Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature. Cells. 2020; 9: 729. doi: 10.3390/cells9030729.

21. Montaldo E., Zotto G.D., Chiesa M.D. Human NK Cell Receptors/Markers: A Tool to Analyze NK Cell Development, Subsets and Function. Cytometry Part A. 2013; 83A: 702-713. doi: 10.1002/cyto.a.22302.

22. Van Acker H.H., Capsomidis A., Smits E.L. et al. CD56 in the Immune System: More Than a Marker for Cytotoxicity? Front. Immunol. 2017; 8: 892. doi: 10.3389/fimmu.2017.00892.

23. Vantourout P. and Hayday A. Six-of-the-best: unique contributions of γδ T cells to immunology. Nat. Rev. Immunol. 2013; 13(2): 88-100. doi:10.1038/nri3384.

24. Gogoi D. and Chiplunkar S.V. Targeting gamma delta T cells for cancer immunotherapy: Bench to bedside. Indian J. Med. Res. 2013; 138: 174-180. doi: PMID: 24434328.

25. Mahnke Y.D., Brodie T.M., Sallusto F. et al. The who’s who of T-cell differentiation: Human memory T-cell subsets. Eur. J. Immunol. 2013; 43: 2797-2809. doi: 10.1002/eji.201343751.

26. Lalor S.J. and McLoughlin R.M. Memory gd T Cells-Newly Appreciated Protagonists in Infection and Immunity. Trends Immunol. 2016; 37(10): 690-702. doi: 10.1016/j.it.2016.07.006.

27. Rosenkranz A., Knight S., Sethi S. et al. Regulatory interactions of αβ and γδ T cells in glomerulonephritis. Kidney Int. 2000; 58(3): 1055-1066. doi: 10.1046/j.1523-1755.2000.00263.x.

28. Falk M.C., Ng G., Zhang G.Y. et al. Infiltration of the kidney by αβ and γδ T cells: effect on progression in IgA nephropathy. Kidney Int. 1995; 47: 177-85. doi: 10.1038/ki.1995.21.

29. Lafayette R.A., Canetta P.A., Rovin B.H. et al. A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. J. Am. Soc. Nephrol. 2017; 28: 1306-13. doi: 10.1681/ASN.2016060640.


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For citations:


Nizheharodava D., Komissarov K., Minchenko E., Adamovich A., Pilotovich V., Zafranskaya M. The function profile of γδТ-lymphocytes in patients with IgA-nephropathy. Nephrology and Dialysis. 2022;24(1):72-81. (In Russ.) https://doi.org/10.28996/2618-9801-2022-1-72-81

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ISSN 1680-4422 (Print)
ISSN 2618-9801 (Online)