# NLRP3 Inflammasome as Potential Predictor of Non-Responsiveness to Immunosuppressive Treatment in Lupus Nephritis

## TL;DR

This study shows that the NLRP3 inflammasome and IL1B levels may predict poor response to treatment in lupus nephritis patients.

## Contribution

The study identifies NLRP3 inflammasome and IL1B as potential biomarkers for non-response to immunosuppressive treatment in lupus nephritis.

## Key findings

- Higher NLRP3 IHC staining was associated with no PERR in lupus nephritis patients.
- IL1B gene expression and IL-1β levels increased significantly in non-responders over 12 months.
- Non-responders had higher IL-1β levels compared to responders at 12 months.

## Abstract

Lupus nephritis (LN) can affect up to 60% of patients with systemic lupus erythematosus (SLE). The NLRP3 inflammasome has been implicated in the pathogenesis of LN. This study aimed to evaluate the role of the NLRP3 inflammasome as a predictor of response to immunosuppressive treatment in patients with active LN. A prospective cohort study was conducted with 20 adult patients with active LN, classes III, IV, and V, from January 2021 to September 2023. Patients were followed up at biopsy (T0) and 6 months (T6) and 12 months (T12) after treatment and classified according to the primary efficacy renal response (PERR) at 12 months. Gene expression of NLRP3, CARD8, CASP1, IL1B, and IL18 was evaluated by RT-qPCR in PBMCs. Immunohistochemistry (IHC) for NLRP3 was performed on kidney tissue. The concentration of cytokine IL-1β was measured using the BD™ Cytometric Bead Array (CBA). The mean age was 31.9 ± 8.3 years, with 19 females and 1 male. After 12 months, 65% of patients achieved PERR. The IHC intensity in inflammatory cells was higher in patients with no PERR (p = 0.0426). In the no-PERR group, the gene expression of IL1B showed a significant increase at T6 (FC = 2.22: p = 0.0037) and T12 (FC = 2.91; p = 0.0001) compared with T0. Relative expression of IL1B was higher in no-PERR patients at T12 compared to the PERR group (p = 0.0477). The no-PERR group also had higher serum IL-1β levels compared to the PERR group at 12 months (2.9 ± 0.5 vs. 2.5 ± 0.7, p = 0.0164). In conclusion, our study evidenced an increase in IL1B expression and IL-1β levels over the 12 months of treatment in no-PERR patients, suggesting a potential biomarker of disease activity. Furthermore, a strong NLRP3 IHC staining score was associated with a higher likelihood of no PERR, highlighting the potential of the NLRP3 inflammasome as a predictor of worse clinical outcomes.