Abstract Background Anti-interferon-γ autoantibodies (AIGAs) are the major cause of adult-onset immunodeficiency leading to disseminated infections. Reducing circulating AIGA titers is essential to restore immune function. This study prospectively evaluated the efficacy of glucocorticoid (GC) therapy in decreasing AIGA levels and improving clinical outcomes. Methods In this prospective observational cohort study (September 2021-July 2025), 58 AIGA-positive patients with confirmed immune damage and stabilized infections were enrolled at the First Affiliated Hospital of Guangxi Medical University. All patients were confirmed to have AIGA-associated immunodeficiency by enzyme-linked immunosorbent assay (ELISA) for antibody titers and Western blot to verify neutralizing capacity. Enrolled Patients received oral prednisone (0.5-1.0 mg/kg/day), tapered over 4-8 weeks. Outcomes included changes in AIGA titers measured by ELISA, immunological markers including immunoglobulin G (IgG), immunoglobulin E (IgE), erythrocyte sedimentation rate (ESR), globulin, acute exacerbations, opportunistic infections, relapse, and survival. Results Baseline AIGA titers were markedly elevated in all patients. Signs of immune dysregulation were common, with elevated IgG and ESR observed in 39 cases (67.24%), followed by elevated IgE in 31 cases (53.45%), cutaneous rash in 28 cases (48.28%), and increased globulin levels in 28 cases (48.28%). The median time from initial diagnosis (acute infection phase) to the onset of immune damage was 6.0 months (interquartile range IQR 1.0-19.5). The median GC treatment duration was 3 months. GC therapy resulted in a 60.3% median reduction in AIGA titers, with 4 patients becoming seronegative. IgG, globulin, ESR, and CRP levels significantly declined, accompanied by symptom improvement. Opportunistic infections occurred in 12%, and 15.5% discontinued therapy due to clinical deterioration. During follow-up, 58.3% relapsed after GC withdrawal, with a median progression-free survival of 4 months. Higher baseline IgG and skin involvement predicted longer remission. Overall mortality was 8.6%, with no severe GC-related adverse events. Conclusion Short-term GC therapy can induce clinical and immunologic remission in AIGA-associated immunodeficiency,particularly by alleviating immune damage. However, relapse is frequent after discontinuation, suggesting that prolonged or maintenance immunosuppressive therapy should be further investigated. This abstract is funded by: Guangxi Key Technologies R Central Leading Local Science and Technology Development Fund Project grant number 2023ZYZX1021; Innovation Project of Guangxi Graduate Education grant number YCBZ2024121
He et al. (Fri,) studied this question.