Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus
BackgroundKeratoconus (KTCN) is the most common corneal ectasia resulting in a conical shape of the cornea. Here, genomic variation in the corneal epithelium (CE) across the keratoconic cone surface in patients with KTCN and its relevance in the functioning of the immune system were assessed.Methods...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197054/full |
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| author | Katarzyna Jaskiewicz Magdalena Maleszka-Kurpiel Magdalena Maleszka-Kurpiel Michał Kabza Justyna A. Karolak Marzena Gajecka Marzena Gajecka |
| author_facet | Katarzyna Jaskiewicz Magdalena Maleszka-Kurpiel Magdalena Maleszka-Kurpiel Michał Kabza Justyna A. Karolak Marzena Gajecka Marzena Gajecka |
| author_sort | Katarzyna Jaskiewicz |
| collection | DOAJ |
| description | BackgroundKeratoconus (KTCN) is the most common corneal ectasia resulting in a conical shape of the cornea. Here, genomic variation in the corneal epithelium (CE) across the keratoconic cone surface in patients with KTCN and its relevance in the functioning of the immune system were assessed.MethodsSamples from four unrelated adolescent patients with KTCN and two control individuals were obtained during the CXL and PRK procedures, respectively. Three topographic regions, central, middle, and peripheral, were separated towards the whole-genome sequencing (WGS) study embracing a total of 18 experimental samples. The coding and non-coding sequence variation, including structural variation, was assessed and then evaluated together with the previously reported transcriptomic outcomes for the same CE samples and full-thickness corneas.ResultsFirst, pathway enrichment analysis of genes with identified coding variants pointed to “Antigen presentation” and “Interferon alpha/beta signaling” as the most overrepresented pathways, indicating the involvement of inflammatory responses in KTCN. Both coding and non-coding sequence variants were found in genes (or in their close proximity) linked to the previously revealed KTCN-specific cellular components, namely, “Actin cytoskeleton”, “Extracellular matrix”, “Collagen-containing extracellular matrix”, “Focal adhesion”, “Hippo signaling pathway”, and “Wnt signaling” pathways. No genomic heterogeneity across the corneal surface was found comparing the assessed topographic regions. Thirty-five chromosomal regions enriched in both coding and non-coding KTCN-specific sequence variants were revealed, with a most representative 5q locus previously recognized as involved in KTCN.ConclusionThe identified genomic features indicate the involvement of innate and adaptive immune system responses in KTCN pathogenesis. |
| first_indexed | 2024-03-13T00:56:55Z |
| format | Article |
| id | doaj.art-3d6ce5702c4a476da474727fcbca5ce6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T00:56:55Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3d6ce5702c4a476da474727fcbca5ce62023-07-06T18:45:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.11970541197054Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconusKatarzyna Jaskiewicz0Magdalena Maleszka-Kurpiel1Magdalena Maleszka-Kurpiel2Michał Kabza3Justyna A. Karolak4Marzena Gajecka5Marzena Gajecka6Institute of Human Genetics, Polish Academy of Sciences, Poznan, PolandOptegra Eye Health Care Clinic in Poznan, Poznan, PolandChair of Ophthalmology and Optometry, Poznan University of Medical Sciences, Poznan, PolandChair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, PolandChair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, PolandInstitute of Human Genetics, Polish Academy of Sciences, Poznan, PolandChair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, PolandBackgroundKeratoconus (KTCN) is the most common corneal ectasia resulting in a conical shape of the cornea. Here, genomic variation in the corneal epithelium (CE) across the keratoconic cone surface in patients with KTCN and its relevance in the functioning of the immune system were assessed.MethodsSamples from four unrelated adolescent patients with KTCN and two control individuals were obtained during the CXL and PRK procedures, respectively. Three topographic regions, central, middle, and peripheral, were separated towards the whole-genome sequencing (WGS) study embracing a total of 18 experimental samples. The coding and non-coding sequence variation, including structural variation, was assessed and then evaluated together with the previously reported transcriptomic outcomes for the same CE samples and full-thickness corneas.ResultsFirst, pathway enrichment analysis of genes with identified coding variants pointed to “Antigen presentation” and “Interferon alpha/beta signaling” as the most overrepresented pathways, indicating the involvement of inflammatory responses in KTCN. Both coding and non-coding sequence variants were found in genes (or in their close proximity) linked to the previously revealed KTCN-specific cellular components, namely, “Actin cytoskeleton”, “Extracellular matrix”, “Collagen-containing extracellular matrix”, “Focal adhesion”, “Hippo signaling pathway”, and “Wnt signaling” pathways. No genomic heterogeneity across the corneal surface was found comparing the assessed topographic regions. Thirty-five chromosomal regions enriched in both coding and non-coding KTCN-specific sequence variants were revealed, with a most representative 5q locus previously recognized as involved in KTCN.ConclusionThe identified genomic features indicate the involvement of innate and adaptive immune system responses in KTCN pathogenesis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197054/fullcorneacorneal epitheliuminflammationnon-coding sequence variationwhole genomeWGS |
| spellingShingle | Katarzyna Jaskiewicz Magdalena Maleszka-Kurpiel Magdalena Maleszka-Kurpiel Michał Kabza Justyna A. Karolak Marzena Gajecka Marzena Gajecka Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus Frontiers in Immunology cornea corneal epithelium inflammation non-coding sequence variation whole genome WGS |
| title | Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus |
| title_full | Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus |
| title_fullStr | Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus |
| title_full_unstemmed | Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus |
| title_short | Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus |
| title_sort | sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus |
| topic | cornea corneal epithelium inflammation non-coding sequence variation whole genome WGS |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197054/full |
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