{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T20:34:44Z","timestamp":1779222884476,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T00:00:00Z","timestamp":1335398400000},"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":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the copy number variation of complement <jats:italic>C4A<\/jats:italic> and <jats:italic>C4B<\/jats:italic> genes in patients with rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DNA samples were obtained from 299 patients and controls and analyzed for copy number variation of total complement <jats:italic>C4, C4A,<\/jats:italic> and <jats:italic>C4B<\/jats:italic> genes. The results were compared by chi\u2010square analysis, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chi\u2010square analysis revealed similar distribution patterns of total <jats:italic>C4<\/jats:italic> alleles in RA patients (n = 160), non\u2010RA patients (n = 88), and healthy controls (n = 51). There was no trend toward <jats:italic>C4A<\/jats:italic> deficiency as in lupus. Significant differences in <jats:italic>C4B<\/jats:italic> distribution were observed in RA patients, in whom an \u223c2\u2010fold increase in the frequency of homozygous and\/or heterozygous <jats:italic>C4B<\/jats:italic> deficiency (0 or 1 allele) (40%) was present relative to non\u2010RA patients or healthy controls (both 21.6%). <jats:italic>C4B<\/jats:italic> deficiency was more frequent in seropositive RA patients than in seronegative RA patients (44% versus 31%). The odds of <jats:italic>C4B<\/jats:italic> deficiency were 2.99 (95% CI 1.58\u20135.65) (<jats:italic>P<\/jats:italic> = 0.0006) in seropositive RA patients relative to non\u2010RA controls. These findings were confirmed in a larger healthy control cohort, yielding an OR of 1.83 (95% CI 1.21\u20132.76) (<jats:italic>P<\/jats:italic> = 0.0056). The association of the shared epitope with <jats:italic>C4B<\/jats:italic> deficiency was significantly greater in seropositive RA patients than in non\u2013seropositive RA controls (96% versus 54.5%) (<jats:italic>P<\/jats:italic> &lt; 0.0001), suggesting that <jats:italic>C4B<\/jats:italic> deficiency interacts with the shared epitope in the development of seropositive RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate a relationship between <jats:italic>C4B<\/jats:italic> copy number variation and RA that approximates that seen between <jats:italic>C4A<\/jats:italic> copy number variation and lupus. The concurrence of <jats:italic>C4B<\/jats:italic> deficiency and the shared epitope in seropositive RA may have broad implications for our understanding of RA pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.33472","type":"journal-article","created":{"date-parts":[[2011,11,10]],"date-time":"2011-11-10T17:49:55Z","timestamp":1320947395000},"page":"1338-1344","source":"Crossref","is-referenced-by-count":37,"title":["Increased frequency of complement <i>C4B<\/i> deficiency in rheumatoid arthritis"],"prefix":"10.1002","volume":"64","author":[{"given":"William F. 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