Peripheral and renal interstitial T-Cell profiles associated with treatment response in lupus nephritis: a retrospective cohort study

Abstract Background Lupus nephritis (LN) treatment response remains heterogeneous. We investigated associations between peripheral/renal T-cell profiles and treatment response, and explored renal T-cell infiltration as a mediator. Methods This retrospective cohort study analyzed data from 424 lupus nephritis patients. Peripheral CD4+/CD8+ T-cell counts were measured via flow cytometry, and renal interstitial infiltrations were assessed immunohistochemically. Associations with treatment response were evaluated using generalized linear and logistic regression models, adjusting for clinicopathological factors. Mediation analysis examined renal T-cell infiltration in connecting peripheral immunity and treatment outcomes. Results The study cohort consisted of 424 patients with biopsy-confirmed LN, predominantly female (84.67%), with a mean age of 30.37 ± 11.18 years. Responders, comprising 68.4% of the cohort, exhibited significantly higher peripheral CD4+ T-cell counts (median 310 vs. 265 cells/μL, P = 0.002) and CD4/CD8 ratios (0.94 vs. 0.73, P 0.01), with adjusted OR of 1.002 (95% CI 1.001–1.003) and 2.462 (95% CI 1.414–4.288), respectively. These associations remained significant after Bonferroni correction. Non-responders showed increased renal interstitial CD8+ T-cell infiltration (148 vs. 80 cells/mm2, P 0.001), while higher renal interstitial CD4/CD8 ratios predicted remission (OR = 8.312, 95% CI 2.593–26.645). The peripheral CD4/CD8 ratio provided incremental predictive value over standard clinical-pathological indices (AUC improvement: 0.711 vs. 0.678, P = 0.022). Mediation analysis revealed that the renal interstitial CD4/CD8 ratio mediated 11.97% of the total effect of the peripheral CD4/CD8 ratio on treatment response (indirect effect β=0.011, P = 0.016). Conclusion Peripheral and renal interstitial T-cell profiles, particularly CD4/CD8 ratios, are significantly associated with treatment response in LN. Renal interstitial T-cells partially mediate the impact of peripheral immune status on clinical outcomes.