{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:31:46Z","timestamp":1786977106943,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007949","name":"Reumatikerf\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007687","name":"Svenska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Copy number variation of the\n                      <jats:italic>C4<\/jats:italic>\n                      complement components,\n                      <jats:italic>C4A<\/jats:italic>\n                      and\n                      <jats:italic>C4B,<\/jats:italic>\n                      has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether\n                      <jats:italic>C4<\/jats:italic>\n                      copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sj\u00f6gren's syndrome (SS), or myositis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using targeted DNA sequencing, we determined the copy number and genetic variants of\n                      <jats:italic>C4<\/jats:italic>\n                      in 2,290 well\u2010characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A prominent relationship was observed between\n                      <jats:italic>C4A<\/jats:italic>\n                      copy number and the presence of SSA\/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0\n                      <jats:italic>C4A<\/jats:italic>\n                      copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2\u201333.3]), whereas a weaker association was seen in patients without SSA\/SSB autoantibodies (OR 3.1 [95% CI 1.7\u20135.5]). The copy number of\n                      <jats:italic>C4<\/jats:italic>\n                      correlated positively with C4 plasma levels. Further, a common loss\u2010of\u2010function variant in\n                      <jats:italic>C4A<\/jats:italic>\n                      leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of\n                      <jats:italic>C4A<\/jats:italic>\n                      . Functionally, we showed that absence of\n                      <jats:italic>C4A<\/jats:italic>\n                      reduced the individuals\u2019 capacity to deposit C4b on immune complexes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We show that a low\n                      <jats:italic>C4A<\/jats:italic>\n                      copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42122","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T01:04:18Z","timestamp":1647911058000},"page":"1440-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Complement\n                    <i>C4<\/i>\n                    Copy Number Variation is Linked to SSA\/Ro and SSB\/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases"],"prefix":"10.1002","volume":"74","author":[{"given":"Christian","family":"Lundtoft","sequence":"first","affiliation":[{"name":"Uppsala University  Uppsala 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