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Innate and adaptive gene single nucleotide polymorphisms associated with susceptibility of severe inflammatory complications in Acanthamoeba keratitis

Citation

Carnt, NA and Pang, I and Burdon, KP and Calder, V and Dart, JK and Subedi, D and Hardcastle, AJ, Innate and adaptive gene single nucleotide polymorphisms associated with susceptibility of severe inflammatory complications in Acanthamoeba keratitis, Investigative Ophthalmology and Visual Science, 62, (3) pp. 1-8. ISSN 0146-0404 (2021) [Refereed Article]


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DOI: doi:10.1167/iovs.62.3.33

Abstract

Purpose: Over a third of patients with Acanthamoeba keratitis (AK) experience severe inflammatory complications (SICs). This study aimed to determine if some contact lens (CL) wearers with AK were predisposed to SICs due to variations in key immune genes.

Methods: CL wearers with AK who attended Moorfields Eye Hospital were recruited prospectively between April 2013 and October 2014. SICs were defined as scleritis and/or stromal ring infiltrate. Genomic DNA was processed with an Illumina Low Input Custom Amplicon assay of 58 single nucleotide polymorphism (SNP) targets across 18 genes and tested for association in PLINK.

Results: Genomic DNA was obtained and analyzed for 105 cases of AK, 40 (38%) of whom experienced SICs. SNPs in the CXCL8 gene encoding IL-8 was significantly associated with protection from SICs (chr4: rs1126647, odds ratio [OR] = 0.3, P = 0.005, rs2227543, OR = 0.4, P = 0.007, and rs2227307, OR = 0.4, P = 0.02) after adjusting for age, sex, steroids prediagnosis, and herpes simplex keratitis (HSK) misdiagnosis. Two TLR-4 SNPs were associated with increased risk of SICs (chr9: rs4986791 and rs4986790, both OR = 6.9, P = 0.01). Th-17 associated SNPs (chr1: IL-23R rs11209026, chr2: IL-1β rs16944, and chr12: IL-22 rs1179251) were also associated with SICs.

Conclusions: The current study identifies biologically relevant genetic variants in patients with AK with SICs; IL-8 is associated with a strong neutrophil response in the cornea in AK, TLR-4 is important in early AK disease, and Th-17 genes are associated with adaptive immune responses to AK in animal models. Genetic screening of patients with AK to predict severity is viable and this would be expected to assist disease management.

Item Details

Item Type:Refereed Article
Keywords:cornea, genetic risk
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:144762
Year Published:2021
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-06-08
Last Modified:2021-06-10
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