Evaluating Single-Nucleotide Polymorphisms in Inflammasome Proteins and Serum Levels of IL-18 and IL-1β in Kidney Interstitial Damage in Anti-Neutrophilic Cytoplasmic Antibody-Associated Vasculitis

Abstract

The inflammasome regulates the innate inflammatory response and is involved in autoimmune diseases. In this study, we explored the levels of IL-18 and IL-1β in serum and urine and the influence of various single-nucleotide polymorphisms (SNPs) on kidney lesions at diagnosis in patients with ANCA-associated vasculitis (AAV) and their clinical outcomes. Ninety-two patients with renal AAV were recruited, and blood and urine were collected at diagnosis. Serum and urine cytokine levels were measured by ELISA. DNA was extracted and genotyped using TaqMan assays for SNPs in several inflammasome genes. Lower serum IL-18 (p = 0.049) and the IL-18 rs187238 G-carrier genotype (p = 0.042) were associated with severe fibrosis. The IL-18 rs1946518 TT genotype was associated with an increased risk of relapse (p = 0.05), whereas GG was related to better renal outcomes (p = 0.031). The rs187238 GG genotype was identified as a risk factor for mortality within the first year after AAV diagnosis, independent of the requirement for dialysis or lung involvement (p = 0.013). We suggest that decreased cytokine levels could be a surrogate marker of scarring and chronicity of the renal lesions, together with the rs187238 GG genotype. If our results are validated, the rs1946518 TT genotype predicts the risk of relapse and renal outcomes during follow-up.

Keywords

• inflammasome
• ANCA-associated vasculitis
• interleukin-18 (IL-18)
• single-nucleotide polymorphisms (SNPs)
• biomarkers