OP-1 Conjunctival genetic ‘fingerprinting’ in ocular mucous membrane pemphigoid

Abstract

Objective Ocular Mucous Membrane Pemphigoid (OcMMP) is a rare disease characterised by chronic autoimmune-driven conjunctival inflammation leading to progressive scarring, and blinding sequelae. The purpose of this study was to characterise the conjunctival gene ‘fingerprint’ involved in the fibrosis signalling pathways in the pathogenesis of OcMMP.

Methods and Analysis Ocular surface gene expression studies were undertaken on conjunctival swabs from OcMMP and age-matched control patients. The NanoString nCounter Human Fibrosis panel (NanoString Technologies Inc.) quantified RNA expression from 770 genes. Differentially expressed genes (DEG) and pathway analysis were determined using HyperScale architecture designed by ROSALIND, Inc. with normalisation, fold changes ( +1.5-fold or £-1.5-fold) and pvalues adjustment (<0.05) using the Benjamini-Hochberg method. Significantly identified genes were aligned to the aldehyde dehydrogenase (ALDH)/retinoic acid fibroblast autoregulation conjunctival scarring signalling pathway, known to be central to immune-mediated mucosal scarring in OcMMP.

Results 6 OcMMP patients (8 eyes, mean age 76.5 (±7.0 SD) years, 6 (66%) male, 3 (50%) biopsy-positive) and 8 agematched cataract patients (15 eyes; age 73.1 (±9.3) years, 3 (37%) male), serving as controls were analysed. Ninety-three DEGs were observed between OcMMP and controls (48 upregulated and 45 downregulated). Of these, the top 10 upregulated DEGs were COL3A1, COL1A1, FN1, TPSAB1/B2, THBS1, SERPINE1, SPP1, COL5A1, OASL and IL1B. 44 pathways that had a global significance score greater or equal to 2, the most significant representing extracellular matrix (ECM) remodelling, synthesis, and degradation. Conclusion The conjunctival genetic ‘fingerprint’ predominantly suggests an activated fibroblastic phenotype in the OcMMP patients and could represent (i) novel targets for drug discovery and (ii) surrogate outcomes/novel biomarkers for the monitoring of disease progression.