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This report investigates how GAD65 autoimmunity can result in multi-organ damage following thymoma resection.

March 16, 2026Frontiers in Immunology0 citationsOpen Access

Case report: Thymoma-associated GAD65 autoimmunity: a unifying mechanism for multi-organ injury involving nervous, endocrine, and renal systems

JSJiaZhong SunWuhan University SSShiqi SunWuhan Sixth Hospital ZSZhiheng SunWuchang University of Technology

Key Points

This report investigates how GAD65 autoimmunity can result in multi-organ damage following thymoma resection.
Clinical evaluation of a 59-year-old male with a history of thymoma and subsequent autoimmune manifestations.
Monitoring of neurological, endocrine, and renal functions alongside serum GAD65 antibody levels.
Use of intravenous immunoglobulin therapy to assess treatment effects on GAD65 levels and clinical symptoms.
Patient developed stiff-person syndrome, autoimmune diabetes, and subclinical hypothyroidism post-thymoma resection.
High titers of GAD65 autoantibodies were consistently linked to multi-organ symptoms.
IVIG treatment resulted in significant reductions of GAD65 antibody levels and improved clinical outcomes.

Abstract

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 μIU/mL), and distal renal tubular acidosis (dRTA) evidenced by severe hypokalemia (K + 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 (500 nmol/L in serum). Epitope mapping identified molecular mimicry between the GAD65 peptide ² 60 PEVKEK² 65 and homologous sequences in renal H + -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.

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