{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:20:13Z","timestamp":1773300013355,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K15508"],"award-info":[{"award-number":["16K15508"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Mother and Child Health Foundation"},{"DOI":"10.13039\/501100008667","name":"SENSHIN Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008667","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nephrotic syndrome (NS) is a renal disease characterized by severe proteinuria and hypoproteinemia. Although several single-gene mutations have been associated with steroid-resistant NS, causative genes for steroid-sensitive NS (SSNS) have not been clarified. While seeking to identify causative genes associated with SSNS by whole-exome sequencing, we found compound heterozygous variants\/mutations (c.524T&amp;gt;C; p.I175T and c.662G&amp;gt;A; p.R221H) of the interleukin-1 receptor accessory protein (IL1RAP) gene in two siblings with SSNS. The siblings\u2019 parents are healthy, and each parent carries a different heterozygous IL1RAP variant\/mutation. Since IL1RAP is a critical subunit of the functional interleukin-1 receptor (IL-1R), we investigated the effect of these variants on IL-1R subunit function. When stimulated with IL-1\u03b2, peripheral blood mononuclear cells from the siblings with SSNS produced markedly lower levels of cytokines compared with cells from healthy family members. Moreover, IL-1R with a variant IL1RAP subunit, reconstituted on a hematopoietic cell line, had impaired binding ability and low reactivity to IL-1\u03b2. Thus, the amino acid substitutions in IL1RAP found in these NS patients are dysfunctional variants\/mutations. Furthermore, in the kidney of Il1rap\u2212\/\u2212 mice, the number of myeloid-derived suppressor cells, which require IL-1\u03b2 for their differentiation, was markedly reduced although these mice did not show significantly increased proteinuria in acute nephrotic injury with lipopolysaccharide treatment. Together, these results identify two IL1RAP variants\/mutations in humans for the first time and suggest that IL1RAP might be a causative gene for familial NS.<\/jats:p>","DOI":"10.1093\/intimm\/dxz081","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T12:15:18Z","timestamp":1576757718000},"page":"283-292","source":"Crossref","is-referenced-by-count":5,"title":["Biallelic variants\/mutations of<i>IL1RAP<\/i>in patients with steroid-sensitive nephrotic syndrome"],"prefix":"10.1093","volume":"32","author":[{"given":"Sou","family":"Niitsuma","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Endocrinology and Vascular Medicine , Sendai, Japan"},{"name":"Department of Pediatrics, Endocrinology and Vascular Medicine , Sendai, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology and Vascular 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Endocrinology and Vascular Medicine , Sendai, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Endocrinology and Vascular Medicine , Sendai, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naonori","family":"Kumagai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology and Vascular Medicine , Sendai, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Niihori","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Tohoku University Graduate School of Medicine , Sendai, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Tohoku University Graduate School of Medicine , Sendai, 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