{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T15:16:37Z","timestamp":1775229397072,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,5,25]],"date-time":"2012-05-25T00:00:00Z","timestamp":1337904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is prevalent in North American Native populations, with a high frequency of multicase families and seropositivity in first\u2010degree relatives. This study was undertaken to determine whether the serum cytokine profile of first\u2010degree relatives of North American Native patients with RA differed from that of individuals with no family history of autoimmunity and whether there was an association with RA autoantibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>North American Native patients with RA (n = 105), their first\u2010degree relatives (n = 273), healthy North American Native controls (n = 200), and Caucasian controls (n = 150) were studied. Serum levels of 42 cytokines were tested using a multiplex laser bead assay. Rheumatoid factor (RF), anti\u2013cyclic citrullinated peptide 2 (anti\u2013CCP\u20102), monocyte chemotactic protein 1 (MCP\u2010l), and high\u2010sensitivity C\u2010reactive protein (hsCRP) were tested by enzyme\u2010linked immunosorbent assay, and HLA\u2013DRB1 alleles by specific primers. Discriminant analysis and logistic regression classified individuals based on their cytokine profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The prevalence of RF (cutoff level predetermined to include 5% of Caucasian controls) and anti\u2010CCP (cutoff level of \u226540 units) was, respectively, 88% and 81% in the RA patients, 34% and 9% in first\u2010degree relatives, and 9% and 4% in North American Native controls; the prevalence of anti\u2010CCP was 0% in Caucasian controls. Levels of most cytokines were highest in RA patients; 17 of 40 cytokines (43%) were significantly higher in first\u2010degree relatives than in controls, including multiple proinflammatory cytokines. Discriminant analysis showed a notable distinction between the groups, with 85% classification accuracy. First\u2010degree relatives had markedly higher MCP\u20101 and hsCRP levels than North American Native controls, but there was no consistent association with RA autoantibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that levels of multiple cytokines and hsCRP are higher in first\u2010degree relatives of North American Native patients with RA compared to individuals from a nonautoimmune background. These data suggest that elevated baseline cytokine levels may be part of the risk profile for developing RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.34449","type":"journal-article","created":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T15:04:13Z","timestamp":1329836653000},"page":"1720-1729","source":"Crossref","is-referenced-by-count":58,"title":["Familial clustering of the serum cytokine profile in the relatives of rheumatoid arthritis patients"],"prefix":"10.1002","volume":"64","author":[{"given":"Hani S.","family":"El\u2010Gabalawy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Smolik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Hart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Elias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keng","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine A.","family":"Peschken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol 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J.","family":"Fritzler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,5,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a113802"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199808)41:8<1464::AID-ART17>3.0.CO;2-X"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.55.2.89"},{"key":"e_1_2_7_5_2","first-page":"1522","article-title":"Family history as a risk factor for rheumatoid arthritis: a case\u2010control study","volume":"24","author":"Koumantaki Y","year":"1997","journal-title":"J Rheumatol"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a008850"},{"key":"e_1_2_7_7_2","first-page":"983","article-title":"Familial seropositive rheumatoid arthritis in North American Native families: effects of shared epitope and cytokine 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