{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:16:24Z","timestamp":1787008584747,"version":"build-2736575974"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012331","name":"LEO Foundation","doi-asserted-by":"publisher","award":["LF-OC-22-001007"],"award-info":[{"award-number":["LF-OC-22-001007"]}],"id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Danish Psoriasis Association Research Foundation"},{"name":"Wehners Foundation"},{"DOI":"10.13039\/501100006286","name":"Aage Bang Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the association between the ERAP1 and ERAP2 genotypes and response to secukinumab treatment in patients with psoriasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ced\/llae128","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T18:32:58Z","timestamp":1712773978000},"page":"1171-1178","source":"Crossref","is-referenced-by-count":6,"title":["<i>ERAP1<\/i>\n                    and\n                    <i>ERAP2<\/i>\n                    gene variants as potential clinical biomarkers of anti-interleukin-17A response in psoriasis\u00a0vulgaris"],"prefix":"10.1093","volume":"49","author":[{"given":"Lasse","family":"Kronborg","sequence":"first","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma Oxlund","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Bertelsen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Hald","family":"Rittig","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Emmanuel","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper Fjellhaugen","family":"Hjuler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Iversen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5665-5212","authenticated-orcid":false,"given":"Claus","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital , Aarhus , Denmark"},{"name":"Department of Clinical Medicine, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"2024091818144995400_llae128-B1","doi-asserted-by":"crossref","first-page":"m1590","DOI":"10.1136\/bmj.m1590","article-title":"National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study","volume":"369","author":"Parisi","year":"2020","journal-title":"BMJ"},{"key":"2024091818144995400_llae128-B2","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(20)32549-6","article-title":"Psoriasis","volume":"397","author":"Griffiths","year":"2021","journal-title":"Lancet"},{"key":"2024091818144995400_llae128-B3","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jaci.2017.07.004","article-title":"Psoriasis pathogenesis and the development of novel targeted immune therapies","volume":"140","author":"Hawkes","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"2024091818144995400_llae128-B4","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/nature05663","article-title":"Pathogenesis and therapy of psoriasis","volume":"445","author":"Lowes","year":"2007","journal-title":"Nature"},{"key":"2024091818144995400_llae128-B5","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.3389\/fimmu.2018.01682","article-title":"The IL-17 family of cytokines in psoriasis: IL-17A and beyond","volume":"9","author":"Brembilla","year":"2018","journal-title":"Front Immunol"},{"key":"2024091818144995400_llae128-B6","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.it.2021.09.005","article-title":"ROR\u03b3t protein modifications and IL-17-mediated inflammation","volume":"42","author":"Kumar","year":"2021","journal-title":"Trends Immunol"},{"key":"2024091818144995400_llae128-B7","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/eji.201646723","article-title":"IL-17 and IL-22 in immunity: driving protection and pathology","volume":"47","author":"Eyerich","year":"2017","journal-title":"Eur J Immunol"},{"key":"2024091818144995400_llae128-B8","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1365-2133.2008.08902.x","article-title":"Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin","volume":"160","author":"Johansen","year":"2009","journal-title":"Br\u00a0J Dermatol"},{"key":"2024091818144995400_llae128-B9","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s12016-018-8702-3","article-title":"The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis","volume":"55","author":"Blauvelt","year":"2018","journal-title":"Clin Rev Allergy Immunol"},{"key":"2024091818144995400_llae128-B10","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.3390\/ijms21041275","article-title":"Interleukin-17A and keratinocytes in psoriasis","volume":"21","author":"Furue","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024091818144995400_llae128-B11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s40265-015-0359-0","article-title":"Secukinumab: first global approval","volume":"75","author":"Sanford","year":"2015","journal-title":"Drugs"},{"key":"2024091818144995400_llae128-B12","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1056\/NEJMoa1314258","article-title":"Secukinumab in plaque psoriasis \u2013 results of two phase 3 trials","volume":"371","author":"Langley","year":"2014","journal-title":"N Engl J Med"},{"key":"2024091818144995400_llae128-B13","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1093\/bjd\/ljac040","article-title":"Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials","volume":"188","author":"Langley","year":"2023","journal-title":"Br J Dermatol"},{"key":"2024091818144995400_llae128-B14","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/bjd.16083","article-title":"HLA-Cw6 and psoriasis","volume":"178","author":"Chen","year":"2018","journal-title":"Br J Dermatol"},{"key":"2024091818144995400_llae128-B15","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.tibs.2013.06.003","article-title":"The MHC I loading complex: a multitasking machinery in adaptive immunity","volume":"38","author":"Hulpke","year":"2013","journal-title":"Trends Bochem Sci"},{"key":"2024091818144995400_llae128-B16","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.humimm.2017.11.010","article-title":"The association of ERAP1 and ERAP2 single nucleotide polymorphisms and their haplotypes with psoriasis vulgaris is dependent on the presence or absence of the HLA-C*06:02 allele and age at disease onset","volume":"79","author":"Wi\u015bniewski","year":"2018","journal-title":"Hum Immunol"},{"key":"2024091818144995400_llae128-B17","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/ni1208","article-title":"Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum","volume":"6","author":"Saveanu","year":"2005","journal-title":"Nat Immunol"},{"key":"2024091818144995400_llae128-B18","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/ng.2667","article-title":"Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci","volume":"45","author":"Cortes","year":"2013","journal-title":"Nat Genet"},{"key":"2024091818144995400_llae128-B19","doi-asserted-by":"crossref","first-page":"e1001157","DOI":"10.1371\/journal.pgen.1001157","article-title":"Balancing selection maintains a form of ERAP2 that undergoes nonsense-\u00admediated decay and affects antigen presentation","volume":"6","author":"Andr\u00e9s","year":"2010","journal-title":"PLOS Genet"},{"key":"2024091818144995400_llae128-B20","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1038\/jid.2014.517","article-title":"A single SNP surrogate for genotyping HLA-C*06:02 in diverse populations","volume":"135","author":"Stuart","year":"2015","journal-title":"J Invest Dermatol"},{"key":"2024091818144995400_llae128-B21","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2024091818144995400_llae128-B22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/sj.cr.7290272","article-title":"SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci","volume":"15","author":"Shi","year":"2005","journal-title":"Cell Res"},{"key":"2024091818144995400_llae128-B23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/cr.2009.33","article-title":"A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis","volume":"19","author":"Li","year":"2009","journal-title":"Cell Res"},{"key":"2024091818144995400_llae128-B24","doi-asserted-by":"crossref","first-page":"adv00579","DOI":"10.2340\/actadv.v101.351","article-title":"Predictors of response to biologics in patients with moderate-to-severe psoriasis: a Danish nationwide cohort study","volume":"101","author":"Schwarz","year":"2021","journal-title":"Acta Derm Venereol"},{"key":"2024091818144995400_llae128-B25","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.jid.2023.01.012","article-title":"Cell-specific, disease-\u00adassociated and variant-linked alterations in expression of ERAP1, ERAP2 and LNPEP aminopeptidases","volume":"143","author":"Marusina","year":"2023","journal-title":"J Invest Dermatol"},{"key":"2024091818144995400_llae128-B26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.molimm.2020.02.020","article-title":"The roles of ERAP1 and ERAP2 in autoimmunity and cancer immunity: new insights and perspective","volume":"121","author":"Babaie","year":"2020","journal-title":"Mol Immunol"},{"key":"2024091818144995400_llae128-B27","doi-asserted-by":"crossref","first-page":"902567","DOI":"10.3389\/fimmu.2022.902567","article-title":"To be or not to be: the case of endoplasmic reticulum aminopeptidase 2","volume":"13","author":"Ku\u015bnierczyk","year":"2022","journal-title":"Front Immunol"},{"key":"2024091818144995400_llae128-B28","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1086\/503821","article-title":"Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene","volume":"78","author":"Nair","year":"2006","journal-title":"Am J Hum Genet"},{"key":"2024091818144995400_llae128-B29","doi-asserted-by":"crossref","first-page":"17203","DOI":"10.1074\/jbc.M117.806976","article-title":"The molecular basis for peptide repertoire selection in the human leucocyte antigen (HLA) C*06:02 molecule","volume":"292","author":"Mobbs","year":"2017","journal-title":"J Biol Chem"}],"container-title":["Clinical and Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ced\/advance-article-pdf\/doi\/10.1093\/ced\/llae128\/58393857\/llae128.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ced\/article-pdf\/49\/10\/1171\/59183536\/llae128.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ced\/article-pdf\/49\/10\/1171\/59183536\/llae128.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T14:15:10Z","timestamp":1726668910000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ced\/article\/49\/10\/1171\/7645632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,15]]},"references-count":29,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,4,15]]},"published-print":{"date-parts":[[2024,9,18]]}},"URL":"https:\/\/doi.org\/10.1093\/ced\/llae128","relation":{},"ISSN":["0307-6938","1365-2230"],"issn-type":[{"value":"0307-6938","type":"print"},{"value":"1365-2230","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,10]]},"published":{"date-parts":[[2024,4,15]]}}}