ERAP1 and ERAP2 Gene Variants as Potential Clinical Biomarkers of Anti-IL-17A Response in Psoriasis Vulgaris

Abstract Background Interleukin (IL)-17A is a proinflammatory cytokine that plays an essential role in the development of psoriasis. Although treatment with anti-IL-17A monoclonal antibodies has demonstrated high efficacy in patients with psoriasis, not all patients respond equally well, highlighting the need for biomarkers to predict treatment response. Specific single-nucleotide polymorphisms (SNPs) in the genes encoding endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) have been associated with psoriasis and other immune-mediated diseases. Objectives To investigate the association between the ERAP1 and ERAP2 genotypes and response to secukinumab treatment in patients with psoriasis. Methods In total, 75 patients with plaque psoriasis were included. All patients were genotyped for the ERAP1 rs27524, rs27044, rs30187, rs2287987 and rs26653 SNPs, the ERAP2 rs2248374 SNP, and the status of the human leucocyte antigen HLA-C*06:02 gene. Results Our results demonstrated that individuals with specific ERAP1 and ERAP2 genotypes had a considerably lower response rate to secukinumab treatment. Patients with the ERAP2 rs2248374 GG genotype had a more than sixfold increased risk of treatment failure compared with patients with the rs2248374 AG or AA genotypes. Stratifying for HLA-C*06:02 status, the ERAP2 GG genotype pointed towards an increased risk of treatment failure among HLA-C*06:02-positive patients, although this was not statistically significant. Conclusions Taken together, this unique study breaks new ground by identifying distinct ERAP1 and ERAP2 gene variants that may serve as potential biomarkers for predicting the treatment response to secukinumab in patients with psoriasis. Notably, our data extend existing knowledge by linking specific ERAP1 and ERAP2 gene variants to treatment outcome.