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Olivia E. O'Leary, Andreas Schoetzau, Ludovic Amruthalingam, Nadine Geber-Hollbach, Kim Plattner, Paul Jenoe, Alexander Schmidt, Christoph Ullmer, Faye M. Drawnel, Sascha Fauser, Hendrik P. N. Scholl, Jakob Passweg, Joerg P. Halter, David Goldblum; Tear Proteomic Predictive Biomarker Model for Ocular Graft Versus Host Disease Classification. Trans. Vis. Sci. Tech. 2020;9(9):3. doi: https://doi.org/10.1167/tvst.9.9.3.
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Diagnosis of ocular graft-versus-host disease (oGVHD) is hampered by a lack of clinically-validated biomarkers. This study aims to predict disease severity on the basis of tear protein expression in mild oGVHD.
Forty-nine patients with and without chronic oGVHD after AHCT were recruited to a cross-sectional observational study. Patients were stratified using NIH guidelines for oGVHD severity: NIH 0 (none; n = 14), NIH 1 (mild; n = 9), NIH 2 (moderate; n = 16), and NIH 3 (severe; n = 10). The proteomic profile of tears was analyzed using liquid chromatography-tandem mass spectrometry. Random forest and penalized logistic regression were used to generate classification and prediction models to stratify patients according to disease severity.
Mass spectrometry detected 785 proteins across all samples. A random forest model used to classify patients by disease grade achieved F1-measure values for correct classification of 0.95 (NIH 0), 0.8 (NIH 1), 0.74 (NIH 2), and 0.83 (NIH 3). A penalized logistic regression model was generated by comparing patients without oGVHD and those with mild oGVHD and applied to identify potential biomarkers present early in disease. A panel of 13 discriminant markers achieved significant diagnostic accuracy in identifying patients with moderate-to-severe disease.
Our work demonstrates the utility of tear protein biomarkers in classifying oGVHD severity and adds further evidence indicating ocular surface inflammation as a main driver of oGVHD clinical phenotype.
Expression levels of a 13-marker tear protein panel in AHCT patients with mild oGVHD may predict development of more severe oGVHD clinical phenotypes.
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