{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:56:24Z","timestamp":1759971384091,"version":"build-2065373602"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T00:00:00Z","timestamp":1461715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Scientist Development Award,"},{"DOI":"10.13039\/100012443","name":"Maryland Stem Cell Research Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012443","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jerome L. Greene Foundation Scholar Award"},{"name":"NIH","award":["R56-AR-2615","P30-AR-3503","DE-12354"],"award-info":[{"award-number":["R56-AR-2615","P30-AR-3503","DE-12354"]}]},{"name":"NIH\/NIAMS","award":["K23 AR061439"],"award-info":[{"award-number":["K23 AR061439"]}]},{"DOI":"10.13039\/100001845","name":"Scleroderma Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001845","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Johns Hopkins Center for Child and Community Health Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the association between anti\u2013interferon\u2010inducible protein 16 (anti\u2013IFI\u201016) antibodies and clinical features of scleroderma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sera from a discovery sample of 94 patients with scleroderma and 47 healthy controls were assayed for anti\u2013IFI\u201016 antibodies by enzyme\u2010linked immunosorbent assay, and associations were examined using regression analyses. Since anti\u2013IFI\u201016 autoantibodies were found to be strongly associated with digital gangrene in the discovery sample, a subsequent case\u2013control study (with subjects matched 1:1 on disease duration) was designed for further exploration. Cases were patients with scleroderma and digital gangrene, while controls were patients with scleroderma and Raynaud's phenomenon alone (n\u2009=\u200939 matched pairs). Nonparametric, unadjusted matched pairs analysis as well as univariate and multivariable conditional logistic regression analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the discovery sample, anti\u2013IFI\u201016 antibodies were more prevalent in patients with scleroderma than in healthy controls (18% versus 2%; <jats:italic>P<\/jats:italic>\u2009=\u20090.01). Patients with anti\u2013IFI\u201016 antibodies, compared to anti\u2013IFI\u201016 antibody\u2013negative patients, were more likely to have limited scleroderma (77% versus 46%; <jats:italic>P<\/jats:italic>\u2009=\u20090.03), a longer disease duration (median 15.2 years [interquartile range 10.6\u201318.3] versus 6.0 years [interquartile range 3.4\u201313.8]; <jats:italic>P<\/jats:italic> &lt; 0.01), digital gangrene (24% versus 4%; <jats:italic>P<\/jats:italic>\u2009=\u20090.02), and a low diffusing capacity for carbon monoxide (DL<jats:sc>co<\/jats:sc>) (<jats:italic>P<\/jats:italic> &lt; 0.01). In the case\u2013control study, 35 (45%) of 78 patients were anti\u2013IFI\u201016 antibody positive. Anti\u2013IFI\u201016 antibody levels were significantly higher in cases with digital gangrene than in matched controls (<jats:italic>P<\/jats:italic>\u2009=\u20090.02). In analyses adjusted for age, cutaneous scleroderma subtype, smoking, and DL<jats:sc>co<\/jats:sc>, high anti\u2013IFI\u201016 antibody levels were associated with the presence of digital gangrene (adjusted odds ratio 2.3, 95% confidence interval 1.0\u20135.6, <jats:italic>P<\/jats:italic>\u2009=\u20090.05). The odds of having digital gangrene increased with higher anti\u2013IFI\u201016 antibody titers, in a dose\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Anti\u2013IFI\u201016 antibodies are associated with digital gangrene in patients with scleroderma. Longitudinal prospective studies exploring anti\u2013IFI\u201016 antibodies as a disease biomarker, and biologic studies investigating the pathogenicity of these antibodies, are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39558","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T11:22:44Z","timestamp":1451388164000},"page":"1262-1271","source":"Crossref","is-referenced-by-count":15,"title":["Anti\u2013Interferon\u2010Inducible Protein 16 Antibodies Associate With Digital Gangrene in Patients With Scleroderma"],"prefix":"10.1002","volume":"68","author":[{"given":"Zsuzsanna H.","family":"McMahan","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ami A.","family":"Shah","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhananjay","family":"Vaidya","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrick M.","family":"Wigley","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antony","family":"Rosen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Casciola\u2010Rosen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,4,27]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_7_2_1","DOI":"10.1056\/NEJMcp013013"},{"doi-asserted-by":"publisher","key":"e_1_2_7_3_1","DOI":"10.1056\/NEJMra0806188"},{"doi-asserted-by":"publisher","key":"e_1_2_7_4_1","DOI":"10.1093\/rheumatology\/kep105"},{"doi-asserted-by":"publisher","key":"e_1_2_7_5_1","DOI":"10.1016\/j.molimm.2011.11.004"},{"doi-asserted-by":"publisher","key":"e_1_2_7_6_1","DOI":"10.1002\/art.22266"},{"doi-asserted-by":"publisher","key":"e_1_2_7_7_1","DOI":"10.1093\/rheumatology\/keq372"},{"doi-asserted-by":"publisher","key":"e_1_2_7_8_1","DOI":"10.1002\/art.1780350614"},{"doi-asserted-by":"publisher","key":"e_1_2_7_9_1","DOI":"10.1002\/art.10775"},{"doi-asserted-by":"publisher","key":"e_1_2_7_10_1","DOI":"10.1089\/107999002320271413"},{"doi-asserted-by":"publisher","key":"e_1_2_7_11_1","DOI":"10.1002\/art.1780230510"},{"doi-asserted-by":"publisher","key":"e_1_2_7_12_1","DOI":"10.1002\/art.38098"},{"key":"e_1_2_7_13_1","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis","volume":"15","author":"LeRoy EC","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_7_14_1","first-page":"2159","article-title":"A disease severity scale for systemic sclerosis: development and testing","volume":"26","author":"Medsger TA","year":"1999","journal-title":"J Rheumatol"},{"key":"e_1_2_7_15_1","first-page":"1281","article-title":"Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis","volume":"22","author":"Clements P","year":"1995","journal-title":"J Rheumatol"},{"doi-asserted-by":"publisher","key":"e_1_2_7_16_1","DOI":"10.1073\/pnas.1313577111"},{"doi-asserted-by":"publisher","key":"e_1_2_7_17_1","DOI":"10.1002\/art.1780401110"},{"doi-asserted-by":"publisher","key":"e_1_2_7_18_1","DOI":"10.1136\/ard.53.8.540"},{"doi-asserted-by":"publisher","key":"e_1_2_7_19_1","DOI":"10.1002\/art.1780350614"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00418-002-0485-0","article-title":"Expression of IFI 16 in epithelial cells and lymphoid tissues","volume":"119","author":"Wei W","year":"2003","journal-title":"Histochem Cell Biol"},{"doi-asserted-by":"publisher","key":"e_1_2_7_21_1","DOI":"10.1189\/jlb.0904507"},{"doi-asserted-by":"publisher","key":"e_1_2_7_22_1","DOI":"10.1093\/intimm\/12.4.415"},{"doi-asserted-by":"publisher","key":"e_1_2_7_23_1","DOI":"10.4172\/2155-9899.1000134"},{"doi-asserted-by":"publisher","key":"e_1_2_7_24_1","DOI":"10.1136\/ard.2007.072686"},{"doi-asserted-by":"publisher","key":"e_1_2_7_25_1","DOI":"10.1016\/j.autrev.2014.10.009"},{"doi-asserted-by":"publisher","key":"e_1_2_7_26_1","DOI":"10.1002\/art.1780270201"}],"container-title":["Arthritis &amp; 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