Genetic basis of defects in immune tolerance underlying the development of autoimmunity
Genetic variants associated with susceptibility to autoimmune disease have provided important insight into the mechanisms responsible for the loss of immune tolerance and the subsequent development of autoantibodies, tissue damage, and onset of clinical disease. Here, we review how genetic variants...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.972121/full |
| _version_ | 1818014991058468864 |
|---|---|
| author | Anne M. Hocking Jane H. Buckner |
| author_facet | Anne M. Hocking Jane H. Buckner |
| author_sort | Anne M. Hocking |
| collection | DOAJ |
| description | Genetic variants associated with susceptibility to autoimmune disease have provided important insight into the mechanisms responsible for the loss of immune tolerance and the subsequent development of autoantibodies, tissue damage, and onset of clinical disease. Here, we review how genetic variants shared across multiple autoimmune diseases have contributed to our understanding of global tolerance failure, focusing on variants in the human leukocyte antigen region, PTPN2 and PTPN22, and their role in antigen presentation and T and B cell homeostasis. Variants unique to a specific autoimmune disease such as those in PADI2 and PADI4 that are associated with rheumatoid arthritis are also discussed, addressing their role in disease-specific immunopathology. Current research continues to focus on determining the functional consequences of autoimmune disease-associated variants but has recently expanded to variants in the non-coding regions of the genome using novel approaches to investigate the impact of these variants on mechanisms regulating gene expression. Lastly, studying genetic risk variants in the setting of autoimmunity has clinical implications, helping predict who will develop autoimmune disease and also identifying potential therapeutic targets. |
| first_indexed | 2024-04-14T06:52:13Z |
| format | Article |
| id | doaj.art-3a0ad08f2b4f49fab9ca5e8505062f96 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T06:52:13Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3a0ad08f2b4f49fab9ca5e8505062f962022-12-22T02:07:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.972121972121Genetic basis of defects in immune tolerance underlying the development of autoimmunityAnne M. HockingJane H. BucknerGenetic variants associated with susceptibility to autoimmune disease have provided important insight into the mechanisms responsible for the loss of immune tolerance and the subsequent development of autoantibodies, tissue damage, and onset of clinical disease. Here, we review how genetic variants shared across multiple autoimmune diseases have contributed to our understanding of global tolerance failure, focusing on variants in the human leukocyte antigen region, PTPN2 and PTPN22, and their role in antigen presentation and T and B cell homeostasis. Variants unique to a specific autoimmune disease such as those in PADI2 and PADI4 that are associated with rheumatoid arthritis are also discussed, addressing their role in disease-specific immunopathology. Current research continues to focus on determining the functional consequences of autoimmune disease-associated variants but has recently expanded to variants in the non-coding regions of the genome using novel approaches to investigate the impact of these variants on mechanisms regulating gene expression. Lastly, studying genetic risk variants in the setting of autoimmunity has clinical implications, helping predict who will develop autoimmune disease and also identifying potential therapeutic targets.https://www.frontiersin.org/articles/10.3389/fimmu.2022.972121/fullgenetic variantsautoimmunityimmune toleranceHLAPTPN2PTPN22 |
| spellingShingle | Anne M. Hocking Jane H. Buckner Genetic basis of defects in immune tolerance underlying the development of autoimmunity Frontiers in Immunology genetic variants autoimmunity immune tolerance HLA PTPN2 PTPN22 |
| title | Genetic basis of defects in immune tolerance underlying the development of autoimmunity |
| title_full | Genetic basis of defects in immune tolerance underlying the development of autoimmunity |
| title_fullStr | Genetic basis of defects in immune tolerance underlying the development of autoimmunity |
| title_full_unstemmed | Genetic basis of defects in immune tolerance underlying the development of autoimmunity |
| title_short | Genetic basis of defects in immune tolerance underlying the development of autoimmunity |
| title_sort | genetic basis of defects in immune tolerance underlying the development of autoimmunity |
| topic | genetic variants autoimmunity immune tolerance HLA PTPN2 PTPN22 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.972121/full |
| work_keys_str_mv | AT annemhocking geneticbasisofdefectsinimmunetoleranceunderlyingthedevelopmentofautoimmunity AT janehbuckner geneticbasisofdefectsinimmunetoleranceunderlyingthedevelopmentofautoimmunity |