Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1
Purpose: In several multicenter clinical trials, HLA-DR was found to be a potential biomarker of dry eye disease (DED)'s severity and prognosis. Given the fact that HLA-DR receptor is a heterodimer consisting in an alpha and a beta chain, we intended to investigate the correlation of inflammato...
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Frontiers Media S.A.
2018-10-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02271/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karima Kessal Karima Kessal Karima Kessal Hong Liang Hong Liang Hong Liang Ghislaine Rabut Ghislaine Rabut Philippe Daull Jean-Sébastien Garrigue Mylene Docquier Stéphane Melik Parsadaniantz Christophe Baudouin Christophe Baudouin Christophe Baudouin Christophe Baudouin Françoise Brignole-Baudouin Françoise Brignole-Baudouin Françoise Brignole-Baudouin |
spellingShingle |
Karima Kessal Karima Kessal Karima Kessal Hong Liang Hong Liang Hong Liang Ghislaine Rabut Ghislaine Rabut Philippe Daull Jean-Sébastien Garrigue Mylene Docquier Stéphane Melik Parsadaniantz Christophe Baudouin Christophe Baudouin Christophe Baudouin Christophe Baudouin Françoise Brignole-Baudouin Françoise Brignole-Baudouin Françoise Brignole-Baudouin Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1 Frontiers in Immunology HLA-DR inflammatory targets NanoString® assay conjunctival imprints dry eye disease |
author_facet |
Karima Kessal Karima Kessal Karima Kessal Hong Liang Hong Liang Hong Liang Ghislaine Rabut Ghislaine Rabut Philippe Daull Jean-Sébastien Garrigue Mylene Docquier Stéphane Melik Parsadaniantz Christophe Baudouin Christophe Baudouin Christophe Baudouin Christophe Baudouin Françoise Brignole-Baudouin Françoise Brignole-Baudouin Françoise Brignole-Baudouin |
author_sort |
Karima Kessal |
title |
Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1 |
title_short |
Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1 |
title_full |
Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1 |
title_fullStr |
Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1 |
title_full_unstemmed |
Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1 |
title_sort |
conjunctival inflammatory gene expression profiling in dry eye disease: correlations with hla-dra and hla-drb1 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-10-01 |
description |
Purpose: In several multicenter clinical trials, HLA-DR was found to be a potential biomarker of dry eye disease (DED)'s severity and prognosis. Given the fact that HLA-DR receptor is a heterodimer consisting in an alpha and a beta chain, we intended to investigate the correlation of inflammatory targets with the corresponding transcripts, HLA-DRA and HLA-DRB1, to characterize specific targets closely related to HLA-DR expressed in conjunctival cells from patients suffering from DED of various etiologies.Methods: A prospective study was conducted in 88 patients with different forms of DED. Ocular symptom scores, ocular-staining grades, tear breakup time (TBUT) and Schirmer test were evaluated. Superficial conjunctival cells were collected by impression cytology and total RNAs were extracted for analyses using the new NanoString® nCounter technology based on an inflammatory human code set containing 249 inflammatory genes.Results: Two hundred transcripts were reliably detected in conjunctival specimens at various levels ranging from 1 to 222,546 RNA copies. Overall, from the 88 samples, 21 target genes showed a highly significant correlation (R > 0.8) with HLA-DRA and HLA-DRB1, HLA-DRA and B1 presenting the highest correlation (R = 0.9). These selected targets belonged to eight family groups, namely interferon and interferon-stimulated genes, tumor necrosis factor superfamily and related factors, Toll-like receptors and related factors, complement system factors, chemokines/cytokines, the RIPK enzyme family, and transduction signals such as the STAT and MAPK families.Conclusions: We have identified a profile of 21 transcripts correlated with HLA-DR expression, suggesting closely regulated signaling pathways and possible direct or indirect interactions between them. The NanoString® nCounter technology in conjunctival imprints could constitute a reliable tool in the future for wider screening of inflammatory biomarkers in DED, usable in very small samples. Broader combinations of biomarkers associated with HLA-DR could be analyzed to develop new diagnostic approaches, identify tighter pathophysiological gene signatures and personalize DED therapies more efficiently. |
topic |
HLA-DR inflammatory targets NanoString® assay conjunctival imprints dry eye disease |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.02271/full |
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doaj-27ce7bbd31db4ed489cd1d6df9bb3d172020-11-25T02:28:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02271407698Conjunctival Inflammatory Gene Expression Profiling in Dry Eye Disease: Correlations With HLA-DRA and HLA-DRB1Karima Kessal0Karima Kessal1Karima Kessal2Hong Liang3Hong Liang4Hong Liang5Ghislaine Rabut6Ghislaine Rabut7Philippe Daull8Jean-Sébastien Garrigue9Mylene Docquier10Stéphane Melik Parsadaniantz11Christophe Baudouin12Christophe Baudouin13Christophe Baudouin14Christophe Baudouin15Françoise Brignole-Baudouin16Françoise Brignole-Baudouin17Françoise Brignole-Baudouin18Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, FranceDepartment of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, Paris, FranceQuinze-Vingts National Ophthalmology Hospital, DHU Sight Restore, INSERM-DGOS CIC 1423, Paris, FranceSorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, FranceDepartment of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, Paris, FranceQuinze-Vingts National Ophthalmology Hospital, DHU Sight Restore, INSERM-DGOS CIC 1423, Paris, FranceDepartment of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, Paris, FranceQuinze-Vingts National Ophthalmology Hospital, DHU Sight Restore, INSERM-DGOS CIC 1423, Paris, FranceSanten SAS, Evry, FranceSanten SAS, Evry, FranceiGE3 Genomics Platform University of Geneva, Geneva, SwitzerlandSorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, FranceSorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, FranceDepartment of Ophthalmology III, Quinze-Vingts National Ophthalmology Hospital, Paris, FranceQuinze-Vingts National Ophthalmology Hospital, DHU Sight Restore, INSERM-DGOS CIC 1423, Paris, FranceDepartment of Ophthalmology, Ambroise Paré Hospital, APHP, University of Versailles Saint-Quentin en Yvelines, Boulogne-Billancourt, FranceSorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, Paris, FranceQuinze-Vingts National Ophthalmology Hospital, DHU Sight Restore, INSERM-DGOS CIC 1423, Paris, FranceSorbonne Paris Cité Université Paris Descartes, Faculté de Pharmacie de Paris, Paris, FrancePurpose: In several multicenter clinical trials, HLA-DR was found to be a potential biomarker of dry eye disease (DED)'s severity and prognosis. Given the fact that HLA-DR receptor is a heterodimer consisting in an alpha and a beta chain, we intended to investigate the correlation of inflammatory targets with the corresponding transcripts, HLA-DRA and HLA-DRB1, to characterize specific targets closely related to HLA-DR expressed in conjunctival cells from patients suffering from DED of various etiologies.Methods: A prospective study was conducted in 88 patients with different forms of DED. Ocular symptom scores, ocular-staining grades, tear breakup time (TBUT) and Schirmer test were evaluated. Superficial conjunctival cells were collected by impression cytology and total RNAs were extracted for analyses using the new NanoString® nCounter technology based on an inflammatory human code set containing 249 inflammatory genes.Results: Two hundred transcripts were reliably detected in conjunctival specimens at various levels ranging from 1 to 222,546 RNA copies. Overall, from the 88 samples, 21 target genes showed a highly significant correlation (R > 0.8) with HLA-DRA and HLA-DRB1, HLA-DRA and B1 presenting the highest correlation (R = 0.9). These selected targets belonged to eight family groups, namely interferon and interferon-stimulated genes, tumor necrosis factor superfamily and related factors, Toll-like receptors and related factors, complement system factors, chemokines/cytokines, the RIPK enzyme family, and transduction signals such as the STAT and MAPK families.Conclusions: We have identified a profile of 21 transcripts correlated with HLA-DR expression, suggesting closely regulated signaling pathways and possible direct or indirect interactions between them. The NanoString® nCounter technology in conjunctival imprints could constitute a reliable tool in the future for wider screening of inflammatory biomarkers in DED, usable in very small samples. Broader combinations of biomarkers associated with HLA-DR could be analyzed to develop new diagnostic approaches, identify tighter pathophysiological gene signatures and personalize DED therapies more efficiently.https://www.frontiersin.org/article/10.3389/fimmu.2018.02271/fullHLA-DRinflammatory targetsNanoString® assayconjunctival imprintsdry eye disease |