{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:13:40Z","timestamp":1771334020888,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008648","name":"Krajowy Naukowy Osrodek Wiodacy","doi-asserted-by":"publisher","award":["30\/2017\/KNOW\/IITD"],"award-info":[{"award-number":["30\/2017\/KNOW\/IITD"]}],"id":[{"id":"10.13039\/501100008648","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005976","name":"Harry J. Lloyd Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005976","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Atopic dermatitis (AD<\/jats:styled-content>) is a common inflammatory skin disease of complex aetiology, with interactions between susceptibility genes and environmental factors. We have previously described a protective effect of the KIR<\/jats:styled-content>2DS<\/jats:styled-content>1<\/jats:italic> gene encoding the natural killer cell receptor, whose ligands are HLA<\/jats:styled-content>\u2010C molecules. Here, we found an association of HLA<\/jats:styled-content>\u2010C*05:01<\/jats:italic> allele with AD<\/jats:styled-content>. KIR<\/jats:styled-content>\u2010HLA<\/jats:styled-content>\u2010C interactions are affected by peptides presented by HLA<\/jats:styled-content>\u2010C. The generation of these peptides is strongly influenced by endoplasmic reticulum aminopeptidases 1 and 2 (ERAP<\/jats:styled-content>1 and ERAP<\/jats:styled-content>2). Expression and activity of ERAP<\/jats:styled-content> molecules depend on the polymorphisms of their genes.<\/jats:p><\/jats:sec>Objective<\/jats:title>Possible associations of several single nucleotide polymorphisms (SNP<\/jats:styled-content>s) in the ERAP<\/jats:styled-content>1<\/jats:italic> and ERAP<\/jats:styled-content>2<\/jats:italic> genes with susceptibility to AD<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Peripheral blood DNA<\/jats:styled-content> isolation from 318 patients and 549 controls. PCR<\/jats:styled-content>\u2010SSO<\/jats:styled-content> or PCR<\/jats:styled-content>\u2010SSP<\/jats:styled-content> for HLA<\/jats:styled-content>\u2010C typing; TaqMan Genotyping Assay for ERAP<\/jats:styled-content> typing.<\/jats:p><\/jats:sec>Results<\/jats:title>Only one SNP<\/jats:styled-content> in the ERAP<\/jats:styled-content>1<\/jats:italic> gene, rs26618T>C, causing the amino acid change Ile276Met, had an association with AD<\/jats:styled-content>. To gain insight on the functional role of this SNP<\/jats:styled-content>, we produced recombinant variants differing only at position 276 (Ile or Met) and tested their aminopeptidase activity against a N\u2010terminally extended precursor LIVDRPVTLV<\/jats:styled-content> of the HLA<\/jats:styled-content>\u2010C*05:01 epitope IVDRPVTLV<\/jats:styled-content>. Both ERAP<\/jats:styled-content>1 variants were able to efficiently generate the epitope, although the 276Ile allotype was able to do this about 50% faster. Furthermore, both variants were quite inefficient in further degradation of the mature epitope. Finally, we found that the effect of 276Met on susceptibility to AD<\/jats:styled-content> was seen only in KIR<\/jats:styled-content>2DS<\/jats:styled-content>1\u2010negative individuals, not protected by this KIR<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Associations of HLA<\/jats:styled-content>\u2010C*05:01 allele and rs26618T>C (Ile276Met) ERAP<\/jats:styled-content>1 polymorphism with AD<\/jats:styled-content>, and a significant difference between these two ERAP<\/jats:styled-content>1 variants in their ability to generate an epitope for the HLA<\/jats:styled-content>\u2010C*05:01 molecule was found.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.15449","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T09:45:33Z","timestamp":1548409533000},"page":"906-911","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Endoplasmic reticulum aminopeptidase 1 polymorphism Ile276Met is associated with atopic dermatitis and affects the generation of an HLA<\/scp>\u2010C associated antigenic epitope in vitro<\/i>"],"prefix":"10.1111","volume":"33","author":[{"given":"W.","family":"Niepiek\u0142o\u2010Miniewska","sequence":"first","affiliation":[{"name":"Laboratory of Immunogenetics and Tissue Immunology Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences Wroc\u0142aw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Mpakali","sequence":"additional","affiliation":[{"name":"National Centre for Scientific Research Demokritos Agia Paraskevi, Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Stratikos","sequence":"additional","affiliation":[{"name":"National Centre for Scientific Research Demokritos Agia Paraskevi, Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0141.","family":"Matusiak","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology Medical University of Wroclaw Wroc\u0142aw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Narbutt","sequence":"additional","affiliation":[{"name":"1st Department of Dermatology and Venereology Medical University of \u0141\u00f3d\u017a \u0141\u00f3d\u017a Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Lesiak","sequence":"additional","affiliation":[{"name":"1st Department of Dermatology and Venereology Medical University of \u0141\u00f3d\u017a \u0141\u00f3d\u017a Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Kuna","sequence":"additional","affiliation":[{"name":"2nd Chair of Internal Diseases Medical University of \u0141\u00f3d\u017a N. 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