{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T22:07:56Z","timestamp":1776722876541,"version":"3.51.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>TREX1<\/jats:italic>\n                      gene is fundamental for the removal of cytosolic DNA and the preservation of immune tolerance. Mutations within this gene are implicated in a range of disorders, such as Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations (RVCL-S), Aicardi-Gouti\u00e8res syndrome (AGS), familial chilblain lupus, and systemic lupus erythematosus (SLE). To the best of our knowledge, this report documents the rare coexistence of\n                      <jats:italic>TREX1<\/jats:italic>\n                      -associated RVCL-S and biopsy-proven lupus nephritis in a single patient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a case involving a middle-aged woman diagnosed with lupus nephritis, confirmed through renal biopsy, who later experienced progressive neurological deficits. Brain imaging demonstrated typical signs of cerebral leukoencephalopathy. Whole-exome sequencing uncovered a pathogenic\n                      <jats:italic>TREX1<\/jats:italic>\n                      mutation (c.811_812dup, p.Asp272Argfs*6), resulting in a diagnosis of genetically confirmed\n                      <jats:italic>TREX1<\/jats:italic>\n                      -associated RVCL-S with an incomplete phenotype, coexisting with lupus nephritis. This case underscores a significant clinical challenge: the use of immunosuppressive therapy for lupus nephritis is hypothesized to potentially exacerbate the vascular complications associated with RVCL-S.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      To the best of our knowledge, this case represents the first documented instance of the\n                      <jats:italic>TREX1<\/jats:italic>\n                      p.Asp272Argfs*6 mutation contributing to the coexistence of RVCL-S and lupus nephritis. This discovery broadens the recognized phenotypic spectrum associated with\n                      <jats:italic>TREX1<\/jats:italic>\n                      -related disorders and underscores a distinct therapeutic challenge in their management. It is important for clinicians to be aware of this new phenotype to ensure prompt diagnosis and tailored treatment strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1758743","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:48:41Z","timestamp":1773902921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["First case of TREX1 mutation-driven retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations coexisting with lupus nephritis: a case report and mechanistic discussion"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenjie","family":"Hao","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Key Laboratory of Xin\u2019An Medicine, Ministry of 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