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

Lasse Kronborg, Emma Oxlund Hansen, Trine Bertelsen, Anne Hald Rittig, Thomas Emmanuel, Sofie Jørgensen, Kasper Fjellhaugen Hjuler, Lars Iversen, Claus Johansen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


BACKGROUND: Interleukin-17A (IL-17A) is a proinflammatory cytokine, playing an essential role in the development of psoriasis. Although treatment with anti-IL-17A monoclonal antibodies has demonstrated high efficacy in psoriasis patients, not all patients respond equally well, highlighting the need for biomarkers to predict treatment response. Specific single nucleotide polymorphisms (SNPs) in the endoplasmatic reticulum aminopeptidase (ERAP) 1 and 2 genes have been associated with psoriasis and other immune-mediated diseases.

OBJECTIVES: We aimed to investigate the association between the ERAP1 and ERAP2 genotypes and response to secukinumab treatment in psoriasis patients.

METHODS: A total of 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 human leukocyte antigen-C*06:02 (HLA-C*06:02) status.

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 G/G genotype had a more than 6-fold increased risk of treatment failure compared with patients with the rs2248374 A/G or -A/A genotypes. Stratifying for HLA-C*06:02 status, the ERAP2 G/G genotype pointed towards an increased risk of treatment failure among HLA-C*06:02-positive patients, although this was not statistically significant.

CONCLUSION: 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 psoriasis patients. Notable, out data extends existing knowledge by linking specific ERAP1 and ERAP2 gene variants to treatment outcome.

Original languageEnglish
JournalClinical and Experimental Dermatology
Publication statusE-pub ahead of print - 15 Apr 2024


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