{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T15:28:46Z","timestamp":1758814126967},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2005,5,23]],"date-time":"2005-05-23T00:00:00Z","timestamp":1116806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,6,15]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Serological profiles for anti-Saccharomyces cerevisiae antibodies (ASCA)\/ perinuclear antineutrophil cytoplasmic antibodies (pANCA) and gene polymorphisms in tumour necrosis factor (TNF)-\u03b1 and intercellular adhesion molecule-1 (ICAM-1) are associated with occurrence and\/or outcome in Crohn's disease. The aim of the study was to characterize the ASCA\/pANCA profile, soluble ICAM-1 expression and single nucleotide gene polymorphisms (SNPs) in TNF-\u03b1 and ICAM-1 genes. Crohn's patients with moderate disease activity were enrolled in a clinical trial of Alicaforsen (ISIS 2302). Peripheral blood samples were collected prospectively for serum studies and for potential analysis of gene polymorphisms. A multivariate analysis was performed to compare treatment effect with the biomarkers studied. Serological testing for ASCA\/pANCA was obtained for 257 patients at baseline: 37% were ASCA+\/pANCA\u2013 (Crohn's pattern), 9% had both markers, 15% were ASCA\u2013\/pANCA+ and 39% had neither marker. When the data were analysed by multiple regression analysis, a trend was found within the Alicaforsen-treated groups for greater rates of remission in the ASCA+\/pANCA\u2013 subgroup versus all other serological profiles (25 versus 14%, P = 0\u00b7068), but not versus the placebo remission rate (18\u00b78%). Gene polymorphisms were assessed in 64 patients, 21 from the placebo group. ICAM-1 assessment revealed no over-representation. However, three unique TNF-\u03b1 SNPs were identified that correlated significantly with remission; sites 290 (P = 0\u00b70253), \u22122735 (P = 0\u00b70317) and \u22123090 (P = 0\u00b70067). Although the overall clinical trial was negative, we have identified a trend towards clinical remission with Alicaforsen therapy in a subgroup of patients with Crohn's disease expressing ASCA+\/pANCA\u2013. Furthermore, we have identified three TNF-\u03b1 SNPs that may also predict a positive therapeutic outcome.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2005.02830.x","type":"journal-article","created":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T12:33:14Z","timestamp":1118838794000},"page":"141-147","source":"Crossref","is-referenced-by-count":7,"title":["Gene polymorphisms and serological markers of patients with active Crohn's disease in a clinical trial of antisense to ICAM-1"],"prefix":"10.1093","volume":"141","author":[{"given":"B R","family":"Yacyshyn","sequence":"first","affiliation":[{"name":"Case Western Reserve University Hospital and Louis Stokes VAMC, Cleveland, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Schievella","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology, Cambridge, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K L","family":"Sewell","sequence":"additional","affiliation":[{"name":"Genentech, Inc., South San Francisco CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A","family":"Tami","sequence":"additional","affiliation":[{"name":"Isis Pharmaceuticals, Carlsbad, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,5,23]]},"reference":[{"key":"2022010817004172800_b1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/35079114","article-title":"A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease","volume":"411","author":"Ogura","year":"2001","journal-title":"Nature"},{"key":"2022010817004172800_b2","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/0092-8674(91)90279-8","article-title":"Leucocyte-endothelial cell recognition: three (or more) steps to specificity and 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