{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T21:02:04Z","timestamp":1794258124984,"version":"4.9.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"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:p>\n                    Thymomas are well-established disruptors of central immune tolerance, yet their capacity to drive systemic autoimmunity via a single autoantigen remains incompletely characterized. We report a 59-year-old male who, following resection of a Masaoka stage IIb type B2 thymoma, developed sequential neurological, endocrine, and renal manifestations over 18 months. Clinical evaluation confirmed stiff-person syndrome (SPS) with axial muscle hypermetabolism on PET-CT, latent autoimmune diabetes (HbA1c 11%), subclinical hypothyroidism (TSH 15.28 \u03bcIU\/mL), and distal renal tubular acidosis (dRTA) evidenced by severe hypokalemia (K\n                    <jats:sup>+<\/jats:sup>\n                    2.4 mmol\/L) and inappropriately alkaline urine (pH 7.5). All three syndromes were associated with persistently high-titer glutamic acid decarboxylase 65 (GAD65) autoantibodies (&amp;gt;500 nmol\/L in serum). Epitope mapping identified molecular mimicry between the GAD65 peptide \u00b2\n                    <jats:sup>60<\/jats:sup>\n                    PEVKEK\u00b2\n                    <jats:sup>65<\/jats:sup>\n                    and homologous sequences in renal H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase and thyroid peroxidase, providing a mechanistic basis for multi-organ cross-reactivity. Treatment with intravenous immunoglobulin (IVIG) led to a 53.6% reduction in serum and an 80% decline in cerebrospinal fluid GAD65 antibody levels, paralleling clinical improvement. This case illustrates how thymoma-induced loss of tolerance to GAD65 can trigger widespread autoimmune injury through conformational epitope spreading, positioning GAD65 as a paraneoplastic pan-autoantigen. High-titer GAD65 antibodies may serve as a biomarker for systemic involvement, supporting early multidisciplinary surveillance in thymoma patients.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1790631","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:48:33Z","timestamp":1773298113000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case report: Thymoma-associated GAD65 autoimmunity: a unifying mechanism for multi-organ injury involving nervous, endocrine, and renal systems"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiazhong","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiheng","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Health and Nursing, Wuchang University of Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liman","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0033-9","article-title":"Development of autoantibodies before the clinical onset of systemic lupus erythematosus","volume":"14","author":"McClain","year":"2018","journal-title":"Nat Rev Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.21037\/jtd-20-2565","article-title":"Autoimmune disorders and paraneoplastic syndromes in thymoma","volume":"12","author":"Misch","year":"2020","journal-title":"J Thorac Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1974.00320200130028","article-title":"The spectrum of diseases associated with thymoma: a review of 255 cases","volume":"134","author":"Enriquez","year":"1974","journal-title":"Arch Intern 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