Characteristics of cell immune response and cytokine status parameters in HIV-infected patients with chronic kidney disease

Introduction: despite advances in the study of the immunopathogenesis of HIV-infection, many aspects of diagnosis of the characteristics of the cellular immune response and the cytokine profile in HIV-infected patients with CKD remain unanswered. Answering these questions can provide a more complete understanding of the mechanisms of kidney damage in HIV-infection. The study aimed to determine the role of immune factors based on the study of the cellular and cytokine immune response in the pathogenesis of kidney damage in HIV-infection. Material and methods: the study involved 30 HIV-infected patients with chronic kidney disease (mean age 31.7±6.2 years). The comparison group consisted of 10 patients with HIV-infection without renal pathology. The control groups of 24 and 15 healthy individuals were used to analyze the immune status and normal cytokine profile, respectively. The study of the cellular composition of lymphocytes of a typical immunogram was performed on a BD FACSCanto II flow cytometer. The determination of the concentration of cytokines in blood serum was carried out by the method of solid-phase ELISA on a multichannel photometer Infinite F50. Results: in patients with HIV-infection kidney damage (presence of proteinuria, decreased GFR) developed against a background of a decrease in the blood content of the T-helper subpopulation of lymphocytes (CD3+/CD4+) (0.2×109/l and 0.4×109/l, respectively, p=0.015) with an increase in the number of cytotoxic T cells (CD3+/CD8+), IFN-γ, IL-10, IL-13, TGF-β and TNF-α. A correlation analysis was found beteween the helper population of T-lymphocytes and the cytokine profibrotic action levels IL-13 that controls the humoral immune response (r=0.671, p=0.034), and TNFα (r=-0.733, p=0.025) that regulates secretion TGFβ. In patients with a decreased level of CD4+ lymphocytes of less than 200 cells/μl and an increase in the concentration of HIV RNA in the blood of more than 100,000 copies/ml in HIV-infected patients with kidney damage, a statistically significant increase in TNFα was observed (with a level of CD4+ lymphocytes of more and less than 200 cells/μl - 19.0 pg/ml and 24.2 pg/ml, respectively, p=0.017; with HIV RNA levels of more and less than 100,000 copies/ml, 24.4 pg/ml and 19.7 pg/ml, respectively, p=0.012) A direct correlation was established between TNFα (r=0.683, p=0.042) and proteinuria, and the inverse with glomerular filtration rate (r=-0.755, p=0.031). Conclusion: in HIV-infected patients with CKD, changes were revealed in the parameters of typical immunograms and cytokine status. Kidney damage developed against the background of a more pronounced drop in the blood T-helper subpopulation of lymphocytes with a predominance of pro-inflammatory and immunosuppressive reactions. The leading role of TNFα in combination with depression of the immune system and high viral load in the formation of kidney damage in HIV-infection has been established.

ВИЧ-инфекция, иммунный ответ, хроническая болезнь почек, маркеры повреждения почек, цитокиновый статус, HIV-infection, immune response, chronic kidney disease, markers of kidney damage, cytokine status

1. Hou J, Nast CC. Changing concepts of HIV infection and renal disease. Curr Opin Nephrol Hypertens. 2018; 27(3): 144-152.

2. Jung O, Haack H.S., Brodt H.R. еt al. Changing spectrum of renal disease in HIV infection. Dtsch Med Wochenschr. 2013; 138(38): 1887-1891.

3. Bertoldi A., De Crignis E., Miserocchi A. еt al. HIV and kidney: a dangerous liaison. New Microbiol. 2017; 40(1): 1-10.

4. Ryom L., Mocroft A., Kirk O. et al. Predictors of advanced chronic kidney disease and end-stage renal disease in HIV-positive persons. AIDS. 2014; 28: 187-199.

5. Ando M., Yanagisawa N. Epidemiology, clinical characteristics, and management of chronic kidney disease in human immunodeficiency virus-infected patients. World J Nephrol. 2015; 4(3): 388-395.

6. Achhra A.C., Nugent M., Mocroft A. еt al. Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals: Recent Developments. Curr HIV/AIDS Rep. 2016; 13(3): 149-57.

7. Lucas G.M., Ross M.J., Stock P.G. et al. Clinical practice guidelines for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014; 59: e96-138.

8. Kooij K.W., Vogt L., Wit F.W. et al. Higher prevalence and faster progression of chronic kidney disease in human immunodeficiency virus-infected middle-aged individuals compared with human immunodeficiency virus-uninfected controls. J Infect Dis. 2017; 216: 622-31.

9. Sereti I., Lane H.C. Immunopathogenesis of Human Immunodeficiency Virus: Implications for Immune-Based Therapies. Clin Infect Dis. 2001; 32: 1738-1755.

10. Moir S., Chun T.W., Fauci A.S. Pathogenic mechanisms of HIV disease. Annu Rev Pathol. 2011; 6: 223-248.

11. Terzieva V.I., Popova D.N., Elenkov I.I. IFN-γ Attenuates Spontaneous Lymphocyte Proliferation by Fuelling Regulatory T Cells in HIV-1-Infected Patients. // Viral Immunol. 2017; 30(3): 157-166.

12. Леви Д. Э. ВИЧ и патогенез СПИДа: Пер. с англ. М.: Научный мир. 2010; 736 с.

13. Кетлинский С.А., Симбирцев А.С. Цитокины. СПб.: Фолиант 2008; 552 с.

14. ВИЧ-инфекция и СПИД: национальное руководство. Под ред. В.В. Покровского. М.: ГЭОТАР-Медиа, 2020. 696 с.

15. Scully E., Alter G. NK Cells in HIV Disease. Curr HIV/AIDS Rep. 2016; 13(2): 85- 94.

16. Doitsh G., Greene W.C. Dissecting how CD4 T cells are lost during HIV infection. Cell Host Microbe. 2016; 19(3): 280-291.

17. Strutz, F., Neilson E.G. New insights into mechanism of fibrosis in immune renal injury. Springer Semin Immunopathol. 2003; 24: 459-476.

18. French M.A., Cozzi-Lepri A., Arduino R.C. еt al. Plasma levels of cytokines and chemokines and the risk of mortality in HIV-infected individuals: a case-control analysis nested in a large clinical trial. AIDS. 2015; 29 (7): 847-851.

19. Conaldi P.G., Bottelli A, Wade-Evans A. еt al. HIV-persistent infection and cytokine induction in mesangial cells: a potential mechanism for HIV-associated glomerulosclerosis. АIDS. 2000; 14 (13): 2045 - 2047.

20. Mikulak J., Singhal P.C. HIV-1 and kidney cells: better understanding of viral interaction. Nephron Exp Nephrol. 2010; 115 (2): 15-21.

21. Alefano M., Crotti А., Vicenzi E. et al. New players in cytokine control of HIV infection. Curr HIV/AIDS. 2008; 5: 27-32.

22. Madrigal-Jimenez H.M., Flores-Flores L., Carrillo Estrada F. et al. High levels of HIV-1 RNA Associated with Early-onset Glomerulopathy in patients with HIV Infection. Mayo Clin Proc. 2007; 82 (9): 1103-1116.

23. Wada T., Yokoyama H., Kobayashi K. Chemokines: new target molecules in renal diseases. Clin Exp Nephrol. 2000; 4: 273-280.

24. Paiardini M., Müller-Trutwin M. HIV-associated chronic immune activation. Immunol Rev. 2013; 254: 78-101.

25. Bottinger E.P., Bitzer M. TGF-β signaling in renal disease. J Am Soc Nephrol. 2002; 13: 2600-2610.

26. Wang H., Li J., Gai Z. et al. TNF-α Deficiency Prevents Renal Inflammation and Oxidative Stress in Obese Mice. Kidney Blood Press Res. 2017; 42 (3): 416-427.

27. Okon K. Tubulo-interstitial changes in glomerulopathy. Prognostic significance. Pol J Pathol. 2003; 4 (3): 163-169.

28. Naicker S., Rahmanian S., Kopp J.B. HIV and chronic kidney disease. Clin Nephrol. 2015; 83 (7): 32-38.

29. Ross M.J. Advances in the pathogenesis of HIV-associated kidney diseases. Kidney Int. 2014; 86: 266-74.