Peptidyl-prolyl cis-trans Isomerase A (PPIA) - a novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis

FIRST PRIZE, COS AWARDS FOR EXCELLENCE IN OPHTHALMIC RESEARCH

Author: Jordan Isenberg
Author Disclosure Block: J. Isenberg: None.

Abstract Body:

Purpose: Ocular toxoplasmosis (OT) is the most common etiology of posterior uveitis. The high incidence of macular scarring associated with OT is a leading cause of visual morbidity. Serum biomarkers of the disease would aid in its diagnosis. This study sought, for the first time, to elucidate serum biomarkers for OT.

Study Design: Shotgun biomarker discovery

Methods: Blood samples were collected from four groups of nine patients each; toxoplasmosis IgG- with no history of uveitis, non-toxoplasmosis uveitic, first episode OT, and symptomatic recurrent OT. Serum was isolated and subjected to proteomics analysis using 2-dimensional gel electrophoresis (GE) and surface-enhanced laser desorption ionization mass spectrometry (SELDI- MS). Selected proteins were further separated by GE and sequenced using tandem MS. Results were directly cross-validated directly with a T. gondii outbreak biomarker database that occurred in a neighboring Brazilian state.

Results: Fifty markers of OT and 46 markers of recurrent disease were discovered by SELDI-MS; 47% were cross-validated; 14 biomarkers were selected for verification by 1-dimensional gel electrophoresis. 2D-GE analysis yielded 57 bands which were selected based on the intensity of the bands, leading to the identification of 20 proteins. 75% of those identified candidates were also found by SELDI-MS. Four candidates were chosen for immunoblotting. Only one serum protein, peptidyl-prolyl cis-trans isomerase A, was validated to be a biomarker of multi-episodic OT by immunoblotting in patient and control samples.

Conclusions: PPIA is a validated marker for multi-episodic OT with significant potential clinical significance