The dysfunction of the E3 ubiquitin ligase TRIM21 in systemic lupus erythematosus (HUM7P.301)

Abstract

Abstract Although the increased expression of type I interferon (IFN)-inducible genes, called “IFN signature”, has been suggested to have important roles in pathogenesis of systemic lupus erythematosus (SLE), its mechanism still remains unclear. Recent studies in vitro or with mice suggest that TRIM21, an autoantigen also called Ro52 or SSA1, is involved in the regulation of type I IFN production as an E3 ubiquitin ligase for IFN regulatory factors (IRFs). Here, we investigated the pathological role of TRIM21 in SLE. We collected peripheral blood mononuclear cells (PBMCs) from 20 patients with SLE and 24 healthy controls (HC). The mRNA levels of TRIM21 and other type I IFN-inducible genes were higher in PBMCs from patients with SLE as compared to HC. Thus, TRIM21 mRNA levels correlated positively with other type I IFN-inducible genes. On the other hand, type I IFN mRNA levels showed a negative correlation with TRIM21 mRNA levels in HC but not in patients with SLE. Consistent with higher TRIM21 mRNA levels, TRIM21 protein levels were higher in SLE patients as compared to HC. After treating with MG-132, the protein levels of IRFs were increased in PBMC from HC, but not in the PBMC from patients with SLE. These results suggest that dysregulation of TRIM21 to function as an E3 ubiquitin ligase for IRF family may be associated with the increased expression of type I IFNs in SLE.