Immunological overlap stratification in anti-GBM disease: prognostic differences and serological correlations-a single-center retrospective cohort study.

Background: Anti-glomerular basement membrane (anti-GBM) disease is not a distinct, isolated entity but rather a condition that frequently overlaps with other autoimmune serological profiles. Most notably, it can coexist with antineutrophil cytoplasmic antibodies (ANCA), alongside a diverse spectrum of additional autoantibodies. Despite the occurrence of such antibody overlap in a subset of patients, their specific clinical manifestations and prognostic implications remain poorly defined and largely elusive. Methods: This study retrospectively enrolled patients diagnosed with anti-GBM disease at the First Affiliated Hospital with Nanjing Medical University between January 2017 and January 2024. Based on serological profiles, enrolled patients were stratified into three cohorts: the classic anti-GBM group (anti-GBM antibodies positive alone), the ANCA-anti-GBM double-positive group, and the anti-GBM-non-ANCA autoantibody overlap group. Clinical, pathological, treatment, and outcome characteristics were systematically compared across the three groups. Additionally, landmark analysis was conducted to assess prognostic discrepancies across distinct time intervals. Results: A total of 67 patients with anti-GBM disease were enrolled in this study, with 30, 18, and 19 cases allocated to the classic anti-GBM group, ANCA-anti-GBM double-positive group, and anti-GBM-non-ANCA autoantibody overlap group, respectively. The ANCA-anti-GBM double-positive group presented with the highest mean age at onset among the three cohorts. A statistically significant difference was detected in baseline anti-GBM antibody titers across the groups (median: 141.20 vs. 104.25 vs. 181.70; interquartile range: 102.90-257.70 vs. 52.15-137.07 vs. 121.05-555.40; p = 0.044). By contrast, no significant differences were noted in terms of other clinical characteristics, renal pathological findings, and therapeutic regimens. Although the overall survival rates showed no statistical discrepancy among the three groups, distinct trends were observed in early survival outcomes: the ANCA-anti-GBM double-positive group had the poorest early survival, followed by the anti-GBM-non-ANCA autoantibody overlap group, while the classic anti-GBM group exhibited the most favorable early survival profile. Conclusion: This study identifies the distinct phenotypic traits of anti-GBM disease with concurrent other autoimmune antibodies, underscoring that sole reliance on anti-GBM antibody titers is inappropriate for prognostic judgment and treatment decision-making. For patients with anti-GBM disease overlapping with non-ANCA autoantibodies, intensive treatment regimens may be justified to achieve more favorable clinical prognosis.