Background: Proliferative lupus nephritis is the biggest risk factor for renal failure requiring renal replacement therapy in SLE patients. Premature immunosenescence is thought to play an important role in the mechanism of proliferative lupus nephritis in SLE patients

Objectives: To determine that premature immunosenescence has an important role in the mechanism of proliferative lupus nephritis in SLE patients

Methods: This study was an observational study with a cross-sectional approach in 61 women aged 16-45 years who were diagnosed with SLE based on the 2012 SLICC criteria. Subjects were recorded for demographic and clinical data and were grouped according to the classification of lupus nephritis from ISN/RPS 2003 through kidney biopsy. Immunosenescence was assessed based on the percentage of CD4 ⁺ CD28 ^- and CD8 ⁺ CD28 ^- T lymphocytes from PBMC using flowcytometry. Serum IFN-γ cytokines were measured using the ELISA method. The severity of lupus nephritis was evaluated by eGFR, proteinuria, activity index, and chronicity of lupus nephritis

Results: Patients with proliferative lupus nephritis had a higher percentage of CD4 ⁺ CD28 ^- , CD8 ⁺ CD28 ^- T lymphocytes and IFN-γ than those without lupus nephritis [median 2.82 (0.54 - 7.69)% vs 0.68 (0.44 - 1.80)%; p=0.037] [mean 18.32 ± 1.01% vs 11.87 ± 6.75%; p=0.043] [median 9.00 (6.15 - 71.07) pg/ml vs 5.55 (4.50 - 12.62) pg/ml; p=0.007]. Cytokine IFN-γ levels had a positive correlation with the percentage of CD4 ⁺ CD28 ^- T lymphocytes (r=0.242; p=0.040). The eGFR value, activity and chronicity index of lupus nephritis were correlated with levels of IFN-γ [(r=-0.403; p=0.004), (r=0.873; p=0.005), (r=0.777; p=0.020)] but not correlated with percentage of CD4 ⁺ CD28 ^- and CD8 ⁺ CD28 ^- T lymphocytes

Conclusion: The percentage of CD4 ⁺ CD28 ^- , CD8 ⁺ CD28 ^- T lymphocytes and levels of IFN-γ cytokine in proliferative lupus nephritis patients were higher than without lupus nephritis. The low eGFR value has a negative correlation with the levels of IFN-γ cytokines but there was no correlation with the high percentage of CD4 ⁺ CD28 ^- , CD8 ⁺ CD28 ^- T lymphocytes

REFERENCES: [1] Żabińska M, Krajewska M, Kościelska-Kasprzak K, Klinger M. CD3(+)CD8(+)CD28(-) T Lymphocytes in Patients with Lupus Nephritis. J Immunol Res. 2016;2016:1058165. doi: 10.1155/2016/1058165. Epub 2016 Jun 30. PMID: 27446964; PMCID: PMC4944066.

[2] Lioulios G, Mitsoglou Z, Fylaktou A, Xochelli A, Christodoulou M, Stai S, Moysidou E, Konstantouli A, Nikolaidou V, Papagianni A, Stangou M. Exhausted but Not Senescent T Lymphocytes Predominate in Lupus Nephritis Patients. Int J Mol Sci. 2022 Nov 11;23(22):13928. doi: 10.3390/ijms232213928. PMID: 36430418; PMCID: PMC9694088.

Acknowledgements: The authors thanks to the patients, Universitas Brawijaya, Dr. Saiful Anwar General Hospital and all of members LAURA study group.

Disclosure of Interests: None declared.