Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients
HLA-DRB1 alleles have been associated with several autoimmune diseases. For anti-citrullinated protein antibody positive rheumatoid arthritis (RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to study the genetic regulation of major histocompatibility complex (M...
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| Format: | Article |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.707217/full |
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| author | Miranda Houtman Espen Hesselberg Lars Rönnblom Lars Klareskog Vivianne Malmström Leonid Padyukov |
| author_facet | Miranda Houtman Espen Hesselberg Lars Rönnblom Lars Klareskog Vivianne Malmström Leonid Padyukov |
| author_sort | Miranda Houtman |
| collection | DOAJ |
| description | HLA-DRB1 alleles have been associated with several autoimmune diseases. For anti-citrullinated protein antibody positive rheumatoid arthritis (RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to study the genetic regulation of major histocompatibility complex (MHC) Class II gene expression in immune cells, we investigated transcriptomic profiles of a variety of immune cells from healthy individuals carrying different HLA-DRB1 alleles. Sequencing libraries from peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells, and CD14+ monocytes of 32 genetically pre-selected healthy female individuals were generated, sequenced and reads were aligned to the standard reference. For the MHC region, reads were mapped to available MHC reference haplotypes and AltHapAlignR was used to estimate gene expression. Using this method, HLA-DRB and HLA-DQ were found to be differentially expressed in different immune cells of healthy individuals as well as in whole blood samples of RA patients carrying HLA-DRB1 SE-positive versus SE-negative alleles. In contrast, no genes outside the MHC region were differentially expressed between individuals carrying HLA-DRB1 SE-positive and SE-negative alleles, thus HLA-DRB1 SE alleles have a strong cis effect on gene expression. Altogether, our findings suggest that immune effects associated with different allelic forms of HLA-DR and HLA-DQ may be associated not only with differences in the structure of these proteins, but also with differences in their expression levels. |
| first_indexed | 2024-12-16T14:15:46Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T14:15:46Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-720717f0a4cd42588ffe447ce3b1a0f12022-12-21T22:28:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.707217707217Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis PatientsMiranda Houtman0Espen Hesselberg1Lars Rönnblom2Lars Klareskog3Vivianne Malmström4Leonid Padyukov5Division of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDepartment of Medical Sciences, Rheumatology, Science for Life Laboratory, Uppsala University, Uppsala, SwedenDivision of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenHLA-DRB1 alleles have been associated with several autoimmune diseases. For anti-citrullinated protein antibody positive rheumatoid arthritis (RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to study the genetic regulation of major histocompatibility complex (MHC) Class II gene expression in immune cells, we investigated transcriptomic profiles of a variety of immune cells from healthy individuals carrying different HLA-DRB1 alleles. Sequencing libraries from peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells, and CD14+ monocytes of 32 genetically pre-selected healthy female individuals were generated, sequenced and reads were aligned to the standard reference. For the MHC region, reads were mapped to available MHC reference haplotypes and AltHapAlignR was used to estimate gene expression. Using this method, HLA-DRB and HLA-DQ were found to be differentially expressed in different immune cells of healthy individuals as well as in whole blood samples of RA patients carrying HLA-DRB1 SE-positive versus SE-negative alleles. In contrast, no genes outside the MHC region were differentially expressed between individuals carrying HLA-DRB1 SE-positive and SE-negative alleles, thus HLA-DRB1 SE alleles have a strong cis effect on gene expression. Altogether, our findings suggest that immune effects associated with different allelic forms of HLA-DR and HLA-DQ may be associated not only with differences in the structure of these proteins, but also with differences in their expression levels.https://www.frontiersin.org/articles/10.3389/fimmu.2021.707217/fullmajor histocompatibility complexRNA-sequencingallelic expressionT cellmonocyterheumatoid arthritis |
| spellingShingle | Miranda Houtman Espen Hesselberg Lars Rönnblom Lars Klareskog Vivianne Malmström Leonid Padyukov Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients Frontiers in Immunology major histocompatibility complex RNA-sequencing allelic expression T cell monocyte rheumatoid arthritis |
| title | Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients |
| title_full | Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients |
| title_fullStr | Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients |
| title_full_unstemmed | Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients |
| title_short | Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients |
| title_sort | haplotype specific expression analysis of mhc class ii genes in healthy individuals and rheumatoid arthritis patients |
| topic | major histocompatibility complex RNA-sequencing allelic expression T cell monocyte rheumatoid arthritis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.707217/full |
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