Antigen Microarray Profiling of Serum Autoantibodies in Pseudoexfoliation Glaucoma

Abstract

Purpose: : Pseudoexfoliation (PXF) syndrome is an age–related disease characterised by abnormal deposition of fibrillar extracellular material in many ocular tissues especially notable in the structures of the anterior chamber of the eye. Glaucoma occurs more commonly in eyes with PXF and has a more serious clinical course and worse prognosis than primary open angle glaucoma. PXF is now also a well recognised systemic disorder where fibrillar material has been found outside the eyes (e.g. skin, lymph nodes, blood vessels). A number of auto antibodies have been identified in some types of glaucoma eg anti–rhodopsin and anti–Ro/SS–A in normal pressure glaucoma. However, no previous examination of autoantibodies in serum of PXF associated glaucoma patients has been carried out.

Methods: : Using protein arrays containing over 10,000 different human recombinant proteins we screened serum samples from patients with PXF in order to identify the antigens of autoantibodies associated with this disease. In this pilot study we profiled the autoantibody repertoire of serum from 12 PXF glaucoma patients, and age and sex–matched controls.

Results: : This revealed approximately 25 potential disease–associated antigens. These antigens included NADH–ubiquinone oxidoreductase. Suppression of expression of the gene encoding this protein in mice induces optic neuropathy causing symptoms similar to Leber hereditary optic neuropathy. We also observed auto–antigens to nerve growth factor alpha enolase, which has been identified as an autoantigen in Hashimoto encephalopathy. Other auto–antigens identified as potentially disease–associated include the cell cycle proteins: inhibitor of growth protein 4 and cyclin dependant kinase inhibitor 1C.

Conclusions: : Protein auto–antibody arrays have identified several antigens which show increased expression in the serum of PXF glaucoma patients.

Keywords: autoimmune disease