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Abstract: SA-PO0811

Myddosome Expression and Kidney Response in Lupus Nephritis: A Longitudinal Study

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • da Silva Júnior, Braziliano Miguel, Instituto Keizo Asami, Recife, PE, Brazil
  • Leite, Maria, Instituto Keizo Asami, Recife, PE, Brazil
  • Oliveira, Camila Barbosa Lyra, Hospital das Clinicas da Universidade Federal de Pernambuco, Recife, PE, Brazil
  • de Lima, Camilla Albertina Dantas, Instituto Keizo Asami, Recife, PE, Brazil
  • Valente, Lucila Maria, Hospital das Clinicas da Universidade Federal de Pernambuco, Recife, PE, Brazil
  • Vajgel, Gisele, Hospital das Clinicas da Universidade Federal de Pernambuco, Recife, PE, Brazil
  • Sandrin-Garcia, Paula S., Instituto Keizo Asami, Recife, PE, Brazil
Background

Uncontrolled innate immune signaling via Toll-like receptors (TLRs) has been associated with the pathogenesis and persistence of lupus nephritis (LN). This study is a longitudinal analysis of TRL7-MyD88 gene expression in patients with active LN from the initial kidney biopsy time point to 12 months of immunosuppressive treatment.

Methods

Twenty patients with active lupus nephritis, class III, IV (+/-V) and V, were followed for 12 months, with samples collected at baseline (t0), 6 (6m) and 12 months (12m). At 12 months, patients were classified according to the presence or absence of primary efficacy renal response (PERR), defined by proteinuria <0.7g/day. Gene expression assays were performed using TaqMan® fluorogenic probes for the genes TLR7, MYD88,IRAK3,TRAF6,IRF5, and NFKB1 using the reference genes RPLP0 and EEF1A1 for data normalization. Relative expression analysis was calculated according to MIQE recommendations, and results were expressed as fold change (FC). Differences between groups were analyzed using Student's t-test and ANOVA, and correlation analysis was performed using Pearson's test.

Results

In the group that achieved PERR (n=13), there was a reduction of MYD88 expression (FC t0 = 1; FC 6m = 0.99; FC 12m = 0.67; p=0.033) and TRAF6 expression (FC t0 = 1; FC 12m = 0.65; p=0.038). Additionally, a direct correlation was observed between TRAF6 expression and 24-hour proteinuria (r=0.76; p=0.006) at t0. And at 6m, TLR7 and SLEDAI expression showed a direct correlation in the no-PERR group (r=0.84; p=0.027).

Conclusion

We demonstrated that patients with PERR exhibit reduced expression of the MYD88 and TRAF6 genes over 12 months of treatment, suggesting modulation of the TLR7-MyD88 pathway in response to immunosuppression. Our findings indicate that regulation of this pathway might be associated with a positive response to treatment.

Relative expression levels in fold change (FC) of genes TLR7, MYD88, IRAK1, TRAF6, IRAK3, NFKB1 and IRF5 in LN patients according to treatment response.