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Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis

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 Moo...

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Autores principales: Carnt, Nicole A., Pang, Ignatius, Burdon, Kathryn P., Calder, Virginia, Dart, John K., Subedi, Dinesh, Hardcastle, Alison J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991962/
https://www.ncbi.nlm.nih.gov/pubmed/33755043
http://dx.doi.org/10.1167/iovs.62.3.33
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author Carnt, Nicole A.
Pang, Ignatius
Burdon, Kathryn P.
Calder, Virginia
Dart, John K.
Subedi, Dinesh
Hardcastle, Alison J.
author_facet Carnt, Nicole A.
Pang, Ignatius
Burdon, Kathryn P.
Calder, Virginia
Dart, John K.
Subedi, Dinesh
Hardcastle, Alison J.
author_sort Carnt, Nicole A.
collection PubMed
description 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.
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spelling pubmed-79919622021-03-30 Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis Carnt, Nicole A. Pang, Ignatius Burdon, Kathryn P. Calder, Virginia Dart, John K. Subedi, Dinesh Hardcastle, Alison J. Invest Ophthalmol Vis Sci Cornea 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. The Association for Research in Vision and Ophthalmology 2021-03-23 /pmc/articles/PMC7991962/ /pubmed/33755043 http://dx.doi.org/10.1167/iovs.62.3.33 Text en Copyright 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Cornea
Carnt, Nicole A.
Pang, Ignatius
Burdon, Kathryn P.
Calder, Virginia
Dart, John K.
Subedi, Dinesh
Hardcastle, Alison J.
Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis
title Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis
title_full Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis
title_fullStr Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis
title_full_unstemmed Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis
title_short Innate and Adaptive Gene Single Nucleotide Polymorphisms Associated With Susceptibility of Severe Inflammatory Complications in Acanthamoeba Keratitis
title_sort innate and adaptive gene single nucleotide polymorphisms associated with susceptibility of severe inflammatory complications in acanthamoeba keratitis
topic Cornea
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991962/
https://www.ncbi.nlm.nih.gov/pubmed/33755043
http://dx.doi.org/10.1167/iovs.62.3.33
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