Högskolan i Skövde

Background: Exfoliative glaucoma (XFG) is characterized by elevated intraocular pressure (IOP) caused by fibrous deposits obstructing aqueous humor drainage, traditionally emphasizing mechanical factors. In this study, we aim to investigate the relationships between clinical parameters and autoimmune activity in exfoliative glaucoma (XFG) patients, and identify patterns of autoantibody reactivity among patient subgroups with differing levels of overall autoimmune activity.

Methods: We analyzed serum autoantibody profiles against 92 antigens in 116 XFG patients using an xMAP suspension bead array. Spearman correlation analysis and PERMANOVA were applied to evaluate relationships between autoantibody reactivity and clinical parameters in glaucoma management. Hierarchical clustering was used to identify clusters of patients based on overall autoantibody reactivity levels, and network analysis using shortest path mapping was utilized to explore potential connections among the proteins associated with the antigens used in this study and other proteins not targeted in this study.

Results: Significant positive correlations were found between the clinical parameter SE and autoantibodies targeting the proteins LOXL3, CYP39A1, and HYOU1. Clustering analysis revealed distinct subgroups of patients with differing overall autoantibody reactivity levels, notably showing significant negative correlations between broad autoantibody profiles and CCT exclusively within the subgroup characterized by higher autoimmune activity. Network analysis identified CTNNB1 as a prominent multi-path intermediary connecting disparate proteins, highlighting potential common regulatory pathways.

Conclusions: This study identifies novel correlations between clinical parameters and autoimmune activity in XFG, suggesting refractive changes and corneal structural characteristics may be influenced by specific immune mechanisms. These findings underscore the value of integrating immunological profiling with clinical glaucoma assessments, potentially enhancing patient stratification and identifying possible therapeutic targets.