NLRP3 Inflammasome Gene Expression Profile and Treatment Response in Lupus Nephritis: A Prospective Cohort Study

Background: Lupus nephritis (LN) is a severe complication of SLE characterized by inflammation and immune complex deposition in the kidneys, leading to progressive renal damage and impaired function. The inflammasome plays a crucial role in the innate immune response, has been implicated in the pathogenesis of LN. The aim of this study was to evaluate de gene expression profile of inflammasome NLRP3 in LN patients according to treatment response. Methods: A prospective cohort study of adult patients with biopsy-proven active LN (class III, IV, and/or V). Clinical, laboratory, and histopathological data were collected at baseline (T0), 6 months (T6), and 12 months (T12) of immunosuppressive treatment. Gene expression of NLRP3, CARD8, CASP1, IL-1B, and IL-18 in peripheral blood mononuclear cells was analyzed using RT-qPCR. Treatment response was classified as primary efficacy renal response (PERR) or non-primary efficacy renal response (no-PERR). Results: Twenty patients with active LN were included in the study. The mean age was 31.9 ± 8.3 years, with 19 females and 1 male. Laboratory evaluation showed median sCr 0.8 (0.7-1.3), median eGFR 103 (54-119), median 24-hour urine protein 3.3 (1.7-4.9). The mean SLEDAI score was 14.6 ± 4.4 and 95% of patients had complement C3 consumption (mean C3 57.2 ± 22.6 mg/dl). Among the 20 patients, 65% achieved PERR after 12 months of therapy. Gene expression analysis revealed that IL-1B expression was significantly higher in the no-PERR group after 12 months. Other inflammasome genes did not show significant changes between the groups. Conclusion: The differential expression of NLRP3 inflammasome components, especially IL-1B, highlights its potential role as a biomarker for predicting treatment response in LN patients. Funding: Private Foundation SupportGene expression of inflammasome NLRP3 in patients with active LN divided by treatment response: primary efficacy renal response (PERR) and with no-PERR. At baseline (T0), 6 months (T6) and 12 months (T12). PERR, primary efficacy renal response