{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:40:45Z","timestamp":1782819645213,"version":"3.54.5"},"reference-count":42,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"unspecified","delay-in-days":76,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Renal Biobank of Jiangsu Provincial Science and Technology Resources Coordination Service Platform","award":["BM2015004-1"],"award-info":[{"award-number":["BM2015004-1"]}]},{"name":"Open Project of Jiangsu Provincial Science and Technology Resources (Clinical Resources) Coordination Service Platform","award":["TC2023B004"],"award-info":[{"award-number":["TC2023B004"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32141004"],"award-info":[{"award-number":["32141004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170739"],"award-info":[{"award-number":["82170739"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82394420"],"award-info":[{"award-number":["82394420"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82394424"],"award-info":[{"award-number":["82394424"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Project of China","award":["2021YFC2501302"],"award-info":[{"award-number":["2021YFC2501302"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2025,3,1]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Pathogenic mutations in genes encoding components of the Ras\/mitogen-activated protein kinase (Ras-MAPK) pathway cause RASopathy. Here, we describe five unrelated patients with SLE carrying mutations associated with RASopathy and investigate the activity of the Ras-MAPK pathway.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Pathogenic variants were identified by whole-exome\/whole-genome sequencing. The activity of the Ras-MAPK pathway in peripheral blood mononuclear cells (PBMC) and kidneys was evaluated using RNA sequencing and datasets from the nephroseq database, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Five (likely) pathogenic variants in four Ras-MAPK genes were identified, including NRAS: c.G38A: p.G13D; ARAF: c.C1435T: p.R479C; KRAS: c.T341C: p.V114A; PTPN11: c.G455A: p.R152H and NRAS: c.G34A: p.G12S. Kidney injury is the main feature, presenting with nephrotic syndrome (2\/5), proteinuria and haematuria (2\/5). Acute kidney injury and rapidly progressive nephritic syndrome were noted in one patient each. Other clinical features included mucocutaneous lesions (5\/5), cardiac involvement (4\/5) and arthralgia (3\/5). Laboratory abnormalities included hypocomplementaemia (5\/5), presence of antiphospholipid antibodies (4\/5), decreased regulatory T cells (3\/3), pancytopenia (3\/5) and persistent monocytosis (2\/5). Kidney biopsy revealed lupus nephritis. Most patients responded well to standard therapy, with the exception of the patient with the NRAS p.G13D mutation who died. The Ras-MAPK pathway was activated in both PBMC and kidney of patients with LN as indicated by increased expression of NRAS, KRAS, RIT1, MRAS, PPP1CB, SHOC2, SOS2 and MAP2K1, as well as decreased expression of negative regulators of the Ras-MAPK pathway, CBL, LZTR1 and NF1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Kidney involvement may be the main feature of the clinical spectrum of RASopathy. Genetic screening should be considered for patients with early onset lupus.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/lupus-2024-001345","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T03:52:07Z","timestamp":1742529127000},"page":"e001345","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Ras-MAPK pathway in patients with lupus nephritis"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct02428309","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Changming","family":"Zhang","sequence":"first","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China"},{"name":"Southeast University School of Medicine, Nanjing, 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Medical School, Nanjing University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxian","family":"Yu","sequence":"additional","affiliation":[{"name":"Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Liang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center of Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhong","sequence":"additional","affiliation":[{"name":"National Clinical Research 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