{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T13:11:21Z","timestamp":1767791481863,"version":"3.49.0"},"reference-count":31,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,8,12]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To evaluate the clinical applicability of autoantibodies (AAbs) measured by ELISA against the angiotensin II type 1 receptor (AT\n                      <jats:sub>1<\/jats:sub>\n                      R) and endothelin-1 type A receptor (ET\n                      <jats:sub>A<\/jats:sub>\n                      R) in systemic sclerosis (SSc) patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Serum samples from n=279\u2009SSc patients from the Leiden Systemic Sclerosis cohort, n=42 patients with primary Raynaud\u2019s phenomenon, n=24 patients with rheumatoid arthritis and n=20 healthy controls were tested for anti-AT\n                      <jats:sub>1<\/jats:sub>\n                      R- and anti-ET\n                      <jats:sub>A<\/jats:sub>\n                      R AAbs. Levels were compared between groups with Mann-Whitney U tests or Kruskal-Wallis tests. Risk ratios and Kaplan-Meier analyses were used to determine associations between AAbs and disease manifestations or all-cause mortality. Analyses were repeated in an independent cohort with n=310\u2009SSc patients from the Radboud University Medical Center.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AAbs against AT\n                      <jats:sub>1<\/jats:sub>\n                      R and ET\n                      <jats:sub>A<\/jats:sub>\n                      R could be detected by ELISA in the sera of all groups tested. Levels were slightly higher in the SSc group compared with the pooled non-SSc group (p=0.043). No associations could be found between anti-AT\n                      <jats:sub>1<\/jats:sub>\n                      R AAbs or anti-ET\n                      <jats:sub>A<\/jats:sub>\n                      R AAbs and disease manifestations or all-cause mortality. In the Radboud cohort, patients with diffuse cutaneous SSc (p=0.001) and interstitial lung disease (p=0.007) had higher median anti-ET\n                      <jats:sub>A<\/jats:sub>\n                      R AAb levels. Patients who died during follow-up had lower levels of anti-AT\n                      <jats:sub>1<\/jats:sub>\n                      R- (p=0.005) and anti-ET\n                      <jats:sub>A<\/jats:sub>\n                      R AAbs (p=0.020).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We confirm positive ELISAs for anti-AT\n                      <jats:sub>1<\/jats:sub>\n                      R AAbs and anti-ET\n                      <jats:sub>A<\/jats:sub>\n                      R AAbs in the sera of several patient groups and healthy controls. Previously described associations with disease manifestations and all-cause mortality could not be confirmed in our cohorts. Based on the current study, the determination of these AAbs is of limited predictive value in clinical practice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005787","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T08:05:18Z","timestamp":1760601918000},"page":"e005787","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Autoantibodies directed against the angiotensin II type 1 receptor and the endothelin-1 type A receptor in patients with systemic sclerosis"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8238-1649","authenticated-orcid":false,"given":"Katherine E","family":"van der Wouden","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands"},{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam University 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E","family":"Liem","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-7520","authenticated-orcid":false,"given":"Tom W J","family":"Huizinga","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9618-6414","authenticated-orcid":false,"given":"Ren\u00e9 E M","family":"Toes","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre E","family":"Voskuyl","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, 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