Innate Immunity Biomarkers for Early Detection of Keratoconus

ABSTRACT

Purpose: To compare toll-like receptors 2 (TLR2) and 4 (TLR4) expression in cells of corneal and conjunctival epithelium between unilateral KC patients and control subjects.

Methods: Prospective cross-sectional case-control study, including 50 unilateral KC patients and 20 control subjects. TLR2 and TLR4 expression was measured with flow cytometry.

Results: Mean expression of TLR2 and TLR4, in corneal and conjunctival cells, was significantly higher in KC than in subclinical and control groups (all p < 0.0001). TLR2 expression in corneal epithelial cells can predict with the highest sensitivity and specificity the probability of KC existence compared to a control (area under the curve 0.995, 95% CI: 0.987–1.000; p < 0.0001). Corneal TLR2 expression also has a predictive capacity to discriminate between subclinical KC and controls (area under the curve 0.989, 95% CI: 0.975–1.000; p < 0.0001).

Conclusions: TLR2 and TLR4 expression in corneal and conjunctival epithelial cells may constitute predictive biomarkers for the early detection of KC.

Keywords:

• Biomarkers
• Innate immunity
• Toll-like receptor 2
• Toll-like receptor 4
• Unilateral keratoconus

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by the Spanish Ministry of Economy and Competitiveness (Instituto de Salud Carlos III) [grant number PI14/00247]; Xunta de Galicia (Consellería de Economía e Industria) [grant number 10 PX113918156PR] and Consellería de Educación [grant number GRC2014/027]; and the European Union program ERFD. T. Sobrino (CPII17/00027) and F. Campos (CP14/00154) are researchers under a research contract with the Miguel Servet Program of Instituto de Salud Carlos III. Similarly, U. Regueiro was awarded a predoctoral Fellowship from the Xunta de Galicia [grant number ED481A-2015/001].