Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes
Abstract Background Ankylosing spondylitis (AS) is a rare inflammatory disorder affecting the spinal joints. Although we know some of the genetic factors that are associated with the disease, the molecular basis of this illness has not yet been fully elucidated, and the genes involved in AS pathogen...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2021-05-01
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| Series: | Egyptian Journal of Medical Human Genetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43042-021-00161-0 |
| _version_ | 1818607320389648384 |
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| author | Rowan AlEjielat Anas Khaleel Amneh H. Tarkhan |
| author_facet | Rowan AlEjielat Anas Khaleel Amneh H. Tarkhan |
| author_sort | Rowan AlEjielat |
| collection | DOAJ |
| description | Abstract Background Ankylosing spondylitis (AS) is a rare inflammatory disorder affecting the spinal joints. Although we know some of the genetic factors that are associated with the disease, the molecular basis of this illness has not yet been fully elucidated, and the genes involved in AS pathogenesis have not been entirely identified. The current study aimed at constructing a gene network that may serve as an AS gene signature and biomarker, both of which will help in disease diagnosis and the identification of therapeutic targets. Previously published gene expression profiles of 16 AS patients and 16 gender- and age-matched controls that were profiled on the Illumina HumanHT-12 V3.0 Expression BeadChip platform were mined. Patients were Portuguese, 21 to 64 years old, were diagnosed based on the modified New York criteria, and had Bath Ankylosing Spondylitis Disease Activity Index scores > 4 and Bath Ankylosing Spondylitis Functional Index scores > 4. All patients were receiving only NSAIDs and/or sulphasalazine. Functional enrichment and pathway analysis were performed to create an interaction network of differentially expressed genes. Results ITM2A, ICOS, VSIG10L, CD59, TRAC, and CTLA-4 were among the significantly differentially expressed genes in AS, but the most significantly downregulated genes were the HLA-DRB6, HLA-DRB5, HLA-DRB4, HLA-DRB3, HLA-DRB1, HLA-DQB1, ITM2A, and CTLA-4 genes. The genes in this study were mostly associated with the regulation of the immune system processes, parts of cell membrane, and signaling related to T cell receptor and antigen receptor, in addition to some overlaps related to the IL2 STAT signaling, as well as the androgen response. The most significantly over-represented pathways in the data set were associated with the “RUNX1 and FOXP3 which control the development of regulatory T lymphocytes (Tregs)” and the “GABA receptor activation” pathways. Conclusions Comprehensive gene analysis of differentially expressed genes in AS reveals a significant gene network that is involved in a multitude of important immune and inflammatory pathways. These pathways and networks might serve as biomarkers for AS and can potentially help in diagnosing the disease and identifying future targets for treatment. |
| first_indexed | 2024-12-16T14:24:53Z |
| format | Article |
| id | doaj.art-a280615c39194e1b96dd449a3aba6052 |
| institution | Directory Open Access Journal |
| issn | 2090-2441 |
| language | English |
| last_indexed | 2024-12-16T14:24:53Z |
| publishDate | 2021-05-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj.art-a280615c39194e1b96dd449a3aba60522022-12-21T22:28:24ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412021-05-0122111310.1186/s43042-021-00161-0Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genesRowan AlEjielat0Anas Khaleel1Amneh H. Tarkhan2Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of PetraDepartment of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of PetraIndependent ResearcherAbstract Background Ankylosing spondylitis (AS) is a rare inflammatory disorder affecting the spinal joints. Although we know some of the genetic factors that are associated with the disease, the molecular basis of this illness has not yet been fully elucidated, and the genes involved in AS pathogenesis have not been entirely identified. The current study aimed at constructing a gene network that may serve as an AS gene signature and biomarker, both of which will help in disease diagnosis and the identification of therapeutic targets. Previously published gene expression profiles of 16 AS patients and 16 gender- and age-matched controls that were profiled on the Illumina HumanHT-12 V3.0 Expression BeadChip platform were mined. Patients were Portuguese, 21 to 64 years old, were diagnosed based on the modified New York criteria, and had Bath Ankylosing Spondylitis Disease Activity Index scores > 4 and Bath Ankylosing Spondylitis Functional Index scores > 4. All patients were receiving only NSAIDs and/or sulphasalazine. Functional enrichment and pathway analysis were performed to create an interaction network of differentially expressed genes. Results ITM2A, ICOS, VSIG10L, CD59, TRAC, and CTLA-4 were among the significantly differentially expressed genes in AS, but the most significantly downregulated genes were the HLA-DRB6, HLA-DRB5, HLA-DRB4, HLA-DRB3, HLA-DRB1, HLA-DQB1, ITM2A, and CTLA-4 genes. The genes in this study were mostly associated with the regulation of the immune system processes, parts of cell membrane, and signaling related to T cell receptor and antigen receptor, in addition to some overlaps related to the IL2 STAT signaling, as well as the androgen response. The most significantly over-represented pathways in the data set were associated with the “RUNX1 and FOXP3 which control the development of regulatory T lymphocytes (Tregs)” and the “GABA receptor activation” pathways. Conclusions Comprehensive gene analysis of differentially expressed genes in AS reveals a significant gene network that is involved in a multitude of important immune and inflammatory pathways. These pathways and networks might serve as biomarkers for AS and can potentially help in diagnosing the disease and identifying future targets for treatment.https://doi.org/10.1186/s43042-021-00161-0Ankylosing spondylitisSpondyloarthritisHLA-DR antigensHLA-DQ antigensITM2ACTLA-4 |
| spellingShingle | Rowan AlEjielat Anas Khaleel Amneh H. Tarkhan Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes Egyptian Journal of Medical Human Genetics Ankylosing spondylitis Spondyloarthritis HLA-DR antigens HLA-DQ antigens ITM2A CTLA-4 |
| title | Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes |
| title_full | Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes |
| title_fullStr | Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes |
| title_full_unstemmed | Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes |
| title_short | Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes |
| title_sort | differential gene expression analysis of ankylosing spondylitis shows deregulation of the hla drb hla dqb itm2a and ctla4 genes |
| topic | Ankylosing spondylitis Spondyloarthritis HLA-DR antigens HLA-DQ antigens ITM2A CTLA-4 |
| url | https://doi.org/10.1186/s43042-021-00161-0 |
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