Detection of Autoantibody Patterns in Sera of Patients with Pseudoexfoliation Syndrome, Pseudoexfoliation Glaucoma and Cataract (Control Group)

Abstract

Purpose: : Up to 55% of patients with pseudoexfoliation syndrome (PEXS) convert to pseudoexfoliation glaucoma (PEXG) within 10 years, but there is no possibility yet to identify those who will be affected. The aim of this study was to analyze autoantibody patterns of patients with PEXS and PEXG, to compare these patterns among both groups and with control subjects (CO) in order to identify markers for patients switching from PEXS to PEXG.

Methods: : Sera of patients with PEXG (n=44), PEXS (n=19) and age matched normal controls with cataract (n=41) were evaluated. For antibody analysis we used protein-microarrays which were prepared by spotting 56 different antigens onto nitrocellulose-coated slides. Arrays were incubated with sera (1:250), and for visualization of the antibody-antigen-reactions arrays were treated with a fluorescence labeled anti-IgG antibody. The signals emitted from secondary antibodies were digitized and the spot intensities were compared using analysis of discriminance.

Results: : PEXG patients showed 6 different significantly increased autoantibody reactivities against heat shock protein (HSP) 70, Neurotrophin 4 and Myelin basic protein in comparison to CO subjects (P≤0.0001). PEXS patients revealed increased reactivities against γ-Synuclein, HSP10 and β-S-Crystallin compared to CO subjects (P≤0.001). γ-Synuclein, proteinkinase c inhibitor and β-S-Crystallin are autoantibodies which differentiate between PEXG and PEXS (P≤0.01). Based on these markers we were able to differentiate between both groups with a sensitivity and specificity of ≥ 90% (AUC of ROC-curve r>0.94). A multivariate analysis of discriminance based on antibody profiles predicted 16.4 % of PEXS subjects as PEXG patients. After splitting the PEXS group in these two parts, we detected Calreticulin, β2 Macroglobulin and Caspase 3 (P≤0.01) as possible biomarkers for conversion to PEXG.

Conclusions: : Differentiation between PEXS and PEXG is maybe possible on the basis of specific autoantibody profiles. This might be useful to identify patients with a high risk for developing PEXG.

Keywords: detection • clinical laboratory testing