Expression and differential regulation of HLA-G isoforms in the retinal pigment epithelial cell line, ARPE-19

Svendsen, Signe Goul; Udsen, Maja Søberg; Daouya, Marina; Funck, Tina; Wu, Ching‐Lien; Carosella, Edgardo D.; LeMaoult, Joël; Hviid, Thomas Vauvert F.; Faber, Carsten; Nissen, Mogens Holst

doi:10.1016/j.humimm.2017.04.007

Cited by 16 publications

(16 citation statements)

References 27 publications

(15 reference statements)

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“…As neovascularization is the key characteristic for wet AMD, this might contribute to progression of the disease from dry to wet AMD. We have previously found that the RPE cell line ARPE‐19 expresses HLA‐G constitutively, and that this expression was upregulated after the cells were stimulated with pro‐inflammatory cytokines . Moreover, the different isoforms of HLA‐G were differentially regulated, suggesting that they might have different functions and that the expression patterns depend on the stimulating factors in the microenvironment rather than the haplotypes examined in this study.…”

Section: Discussionsupporting

confidence: 91%

“…Analysis of the gene expression in RPE/choroid from donor eyes confirmed the results from our previous study showing the expression of HLA‐G in the RPE cell line ARPE‐19 …”

Section: Resultsmentioning

confidence: 99%

“…In a previous study, we have shown that HLA‐G was expressed in a retinal pigment epithelium (RPE) cell line . The RPE is placed between the retina and the choroid and contributes to the immune privilege of the eye by multiple mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Extended HLA‐G haplotypes in patients with age‐related macular degeneration

Svendsen

Nilsson

Djurisic

et al. 2018

HLA

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The study aims to determine if genetic polymorphisms in the human leukocyte antigen (HLA)-G gene are associated with age-related macular degeneration (AMD). HLA-G is important for immunological tolerance, and it is also known to have angiogenic effects. Polymorphisms in the 5'-upstream regulatory region (URR) and 3'-untranslated region (UTR) of HLA-G have been associated with a number of diseases, especially with respect to a 14 bp insertion/deletion (ins/del) polymorphism in the 3'UTR. Full gene sequencing was performed on a cohort of 146 AMD patients and 63 healthy controls aged 60 years or older and HLA-G haplotypes were determined. Analyses were performed on a publicly available gene expression dataset from the NCBI GEO database (accession number GSE29801) from which expression data for HLA-G, -C and -A were extracted. Analysis of the GEO dataset showed that both HLA-G and -C was expressed in the back of the eye and that expression was upregulated in the macular area of AMD. No differences were observed between patients and controls when analysing the distribution of haplotypes in the HLA-G promoter, coding region, 3'UTR or the 14 bp ins/del polymorphism of the 3'UTR. The increased expression of HLA-G in the macula of AMD patients indicates a role of HLA-G in the micro environment as part of the AMD pathogenesis. This is supported by the expression of HLA-C, which has previously been shown to play a role in AMD. The HLA-G haplotype distribution did not display any differences between AMD patients and controls. This article is protected by copyright. All rights reserved.

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Section: Discussionsupporting

confidence: 91%

“…Analysis of the gene expression in RPE/choroid from donor eyes confirmed the results from our previous study showing the expression of HLA‐G in the RPE cell line ARPE‐19 …”

Section: Resultsmentioning

confidence: 99%

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Extended HLA‐G haplotypes in patients with age‐related macular degeneration

Svendsen

Nilsson

Djurisic

et al. 2018

HLA

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“…Additional isoforms have been recently described by RNAseq assays in clear cell renal cell carcinoma . Some insights on the differential regulation of expression of HLA‐G isoforms in response to stimulation with pro‐inflammatory cytokines in retinal pigment epithelium cells of the eye have been also provided . However, tissue‐specific patterns of splicing and function of the different isoforms are yet to be understood .…”

Section: The Hla‐g Gene and Hla‐g Moleculementioning

confidence: 99%

The role of HLA‐G in parasitic diseases

Sabbagh

Sonon

Sadissou

et al. 2018

HLA

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Little attention has been devoted to the role of HLA-G gene and molecule on parasitic disorders, and the available studies have focused on malaria, African and American trypanosomiasis, leishmaniosis, toxoplasmosis and echinococcosis. After reporting a brief description regarding the role of the cells of innate and adaptive immune system against parasites, we reviewed the major features of the HLA-G gene and molecule and the role of HLA-G on the major cells of immune system. Increased levels of soluble HLA-G (sHLA-G) have been observed in patients presenting toxoplasmosis and in the active phase of echinococcosis. In addition, increased sHLA-G has also been associated with increased susceptibility to malaria and increased susceptibility to develop human African trypanosomiasis (HAT). In contrast, decreased membrane-bound HLA-G has been reported in placenta of patients infected with Plasmodium falciparum and in heart and colon of patients presenting Chagas disease. The 3' untranslated region of the HLA-G gene has been the main focus of studies on malaria, HAT and Chagas disease, exhibiting distinct patterns of associations. Considering that HLA-G is an immune checkpoint molecule, inhibiting the activity of several cells of the immune system, the excessive neoexpression and the increased sHLA-G levels together with the decreased constitutive tissue expression of membrane-bound HLA-G may be detrimental to the host infected with parasite agents.

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“…The top 3 genes (CFHR1, CGHR3, and HTRA1) are known to be associ- ated with AMD in MalaCards, as well as the gene CFH (ranked 18). In addition, 9 other genes (PILRA [27,36], ZFP57 [37], BTBD16 [38][39][40], HLA-G [41], ZBTB41 [42,43], DMBT1 [44], RDH5 [45,46], GPR108 [37,47], C4B [48,49]) are reported as AMD-related in the literature. For example, the RDH5 gene encodes the protein retinol dehydrogenase 5, which is an enzyme catalyzing the biosynthesis of 11-cis retinaldehyde.…”

Section: Application Of Gep-hmrf To Gwass Of Complex Human Phenotypesmentioning

confidence: 99%

Inferring Gene-Disease Association by an Integrative Analysis of eQTL Genome-Wide Association Study and Protein-Protein Interaction Data

et al. 2018

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Objectives: Genome-wide association studies (GWASs) have revealed many candidate SNPs, but the mechanisms by which these SNPs influence diseases are largely unknown. In order to decipher the underlying mechanisms, several methods have been developed to predict disease-associated genes based on the integration of GWAS and eQTL data (e.g., Sherlock and COLOC). A number of studies have also incorporated information from gene networks into GWAS analysis to reprioritize candidate genes. Methods: Motivated by these two different approaches, we have developed a statistical framework to integrate information from GWAS, eQTL, and protein-protein interaction (PPI) data to predict disease-associated genes. Our approach is based on a hidden Markov random field (HMRF) model, and we called the resulting computational algorithm GeP-HMRF (a GWAS-eQTL-PPI-based HMRF). Results: We compared the performance of GeP-HMRF with Sherlock, COLOC, and NetWAS methods on 9 GWAS datasets, using the disease-related genes in the MalaCards database as the standard, and found that GeP-HMRF significantly improves the prediction accuracy. We also applied GeP-HMRF to an age-related macular degeneration disease (AMD) dataset. Among the top 50 genes predicted by GeP-HMRF, 7 are reported by the MalaCards database to be AMD-related with an enrichment p value of 3.61 × 10^–119. Among the top 20 genes predicted by GeP-HMRF, CFHR1, CGHR3, HTRA1, and CFH are AMD-related in the MalaCards database, and another 9 genes are supported by the literature. Conclusions: We built a unified statistical model to predict disease-related genes by integrating GWAS, eQTL, and PPI data. Our approach outperforms Sherlock, COLOC, and NetWAS in simulation studies and 9 GWAS datasets. Our approach can be generalized to incorporate other molecular trait data beyond eQTL and other interaction data beyond PPI.

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Expression and differential regulation of HLA-G isoforms in the retinal pigment epithelial cell line, ARPE-19

Cited by 16 publications

References 27 publications

Extended HLA‐G haplotypes in patients with age‐related macular degeneration

Extended HLA‐G haplotypes in patients with age‐related macular degeneration

The role of HLA‐G in parasitic diseases

Inferring Gene-Disease Association by an Integrative Analysis of eQTL Genome-Wide Association Study and Protein-Protein Interaction Data

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