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Exp Eye Res. 2018 Dec;177:104-111. doi: 10.1016/j.exer.2018.07.029. Epub 2018 Jul 29.

Peptidyl-prolyl cis-trans isomerase A - A novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis.

Author information

1
The Henry C. Witleson Ocular Pathology Laboratory, McGill University, Montréal, Québec, Canada; Department of Ophthalmology, University of Montreal, Montréal, Québec, Canada; Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
2
Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada; National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
3
The Henry C. Witleson Ocular Pathology Laboratory, McGill University, Montréal, Québec, Canada; Vision Institute, Department of Ophthalmology, Federal University of São Paulo, São Paulo, SP, Brazil.
4
Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, U.S. Food and Drug Administration, Laurel, MD, USA.
5
Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada; National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada. Electronic address: momar.ndao@mcgill.ca.

Abstract

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 by mass spectrometry. Blood samples were collected from four groups of nine patients each; toxoplasmosis IgG-with no history of uveitis, non-toxoplasmosis uveitis, first episode OT, and symptomatic recurrent OT. Serum was isolated and subjected to proteomics analysis using 2-dimensional gel electrophoresis (2D-GE) and surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS). Selected proteins were further separated by SDS-PAGE and sequenced using tandem MS. Results were cross-validated with a T. gondii outbreak biomarker database that occurred in Brazil. Fifty markers of OT and 46 markers of recurrent disease were discovered by SELDI-MS of which 30 and 15, respectively, were cross-validated. 2D-GE analysis yielded 57 bands, selected based on the intensity of the bands, leading to the identification of 20 proteins. Eleven of those identified candidates were also found by SELDI-MS. Four candidates were chosen for immunoblotting. One serum protein, peptidyl-prolyl cis-trans isomerase A (PPIA), was confirmed as a biomarker of multi-episodic OT by immunoblotting in patients. PPIA can identify the patient with active recurrent OT from acute OT, other forms of uveitis and other parasitic infections. A validated PPIA assay may have a role in the diagnosis of the atypical OT patient before more invasive anterior chamber or vitreous tap is performed for PCR analysis or for Goldmann-Witner coefficient calculations. Base-line PPIA levels need to be studied to understand its possible use when deciding for prophylactic antibiotic use in the immunosuppressed sero-positive patient.

KEYWORDS:

Biomarker discovery; Diagnostic; Ocular toxoplasmosis; Plasma serum; SELDI-MS; Top-down proteomics

PMID:
30063883
DOI:
10.1016/j.exer.2018.07.029
[Indexed for MEDLINE]

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