Neutralizing anti-GM-CSF autoantibodies as a risk factor of orbital extension and blindness in chronic invasive Aspergillus rhinosinusitis: A retrospective observational study.

OBJECTIVES

To investigate the role of antigranulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in Aspergillus infections.

METHODS

A retrospective study (2017-2025) was conducted to determine the prevalence and clinical significance of neutralizing anti-GM-CSF autoantibodies in adult patients with chronic invasive Aspergillus rhinosinusitis (CIARS) and chronic pulmonary aspergillosis (CPA). Neutralizing capacity of anti-GM-CSF autoantibodies was confirmed via STAT5 phosphorylation inhibition assays. Firth's penalized likelihood logistic regression was used to identify independent risk factors for blindness in CIARS.

RESULTS

High-titer neutralizing autoantibodies were detected in 6.0% (8/133) of patients with CIARS, significantly higher than in patients with CPA (1.3% [3/224]; P = 0.022) and healthy controls (0%; P = 0.023). Most patients with autoantibodies were phenotypically immunocompetent. In the CIARS cohort, autoantibody positivity was strongly associated with orbital involvement (87.5% vs 36.8%; P = 0.007) and blindness (50.0% vs 15.2%; P = 0.030). Multivariable Firth regression identified anti-GM-CSF autoantibody positivity as an independent driver of blindness (adjusted OR 6.55, 95% CI: 1.37-31.32; P = 0.019), distinct from the risk posed by sphenoid sinus involvement.

CONCLUSIONS

Neutralizing anti-GM-CSF autoantibodies define a specific, high-risk immunologic endotype in CIARS, characterized by aggressive orbital extension in otherwise immunocompetent hosts. Routine screening for anti-GM-CSF autoantibodies in invasive Aspergillus rhinosinusitis could facilitate early risk stratification and prompt aggressive intervention to preserve vision.