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Panthagani, Jesse; Suleiman, Kusy; Vincent, Rachel C.; Ong, Hon Shing; Wallace, Graham R.; Rauz, Saaeha
The ocular surface, October 2023, 2023-Oct, 2023-10-00, 20231001, Letnik: 30Journal Article
Ocular Mucous Membrane Pemphigoid (OcMMP) is an orphan disease characterized by chronic autoimmune-driven conjunctival inflammation leading to progressive scarring, debilitating symptoms, and blinding sequelae. This feasibility study aims to demonstrate conjunctival genetic transcriptomic analyses as a putative tool for interrogation of pathogenic signaling pathways in OcMMP. Conjunctival RNA profiling using the NanoString nCounter Human Fibrosis panel was undertaken on RNA extracted from conjunctival swabs obtained from 6 MMP patients (8 eyes; 4 M/2F; median age 78 range 64–84 years); and 8 age-matched control participants (15 eyes; 3 M/5F; median age 69.5 range 69–88 years). Data from 770 genes were analyzed with ROSALIND HyperScale architecture and stratified according to the level of clinically visible bulbar conjunctival inflammation. Normalization, fold-changes (≥+1.5-fold or ≤ −1.5-fold) and p-values adjustment (<0.05) using the Benjamini-Hochberg method were calculated. 93 differentially expressed genes (DEGs) were observed between OcMMP versus controls of which 48 were upregulated, and 45 downregulated. The top 4 upregulated DEGs represented fibrosis (COL3A1, COL1A1, FN1 and THBS1) while the key under-expressed genes (SCIN, HMGS2, XCL1/2) were indicative of ocular surface failure (goblet cell loss, keratinization, vulnerability to secondary infections). Forty-four pathways had a global significance score ≥2, the most significant being those related to extracellular matrix (ECM) remodeling, synthesis, and degradation. These pathways were accentuated in eyes with visible inflammation. NanoString methodology acquired via a simple conjunctival swab identifies profibrotic genes in OcMMP group and differentiates inflamed eyes. Longitudinal sampling and following investigative intervention will further mechanistic insight and development of novel biomarkers to monitor disease progression.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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