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3. Haplotype-Specific Expression Analysis of MHC Class II Genes in Healthy Individuals and Rheumatoid Arthritis Patients

Author

Houtman, Miranda, Hesselberg, Espen, Rönnblom, Lars, Klareskog, Lars, Malmstrom, Vivianne, Padyukov, Leonid, Houtman, Miranda, Hesselberg, Espen, Rönnblom, Lars, Klareskog, Lars, Malmstrom, Vivianne, and Padyukov, Leonid

Abstract

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.

Published
2021
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6. Additional file 5: of T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients

Author

Houtman, Miranda, Ekholm, Louise, Hesselberg, Espen, Chemin, Karine, Malmström, Vivianne, Reed, Ann, Lundberg, Ingrid, and Padyukov, Leonid

Abstract

Gene Ontology biological processes for the differentially expressed genes in CD8+ T cells of PM and DM patients. Table S10 shows the genes mapped to the enriched GO biological processes for the differentially expressed genes in CD8+ T cells of PM and DM patients. (DOCX 17 kb)

Published
2018
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7. Additional file 4: of T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients

Author

Houtman, Miranda, Ekholm, Louise, Hesselberg, Espen, Chemin, Karine, Malmström, Vivianne, Reed, Ann, Lundberg, Ingrid, and Padyukov, Leonid

Subjects
health care economics and organizations
Abstract

Differentially expressed genes for CD8+ T cells of PM and DM patients. Tables S8 and S9 provide differentially expressed genes for CD8+ T cells of PM and DM patients at analytical stage 1 (including potential outliers) and analytical stage 2 (excluding potential outliers), respectively. (DOCX 106 kb)

Published
2018
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8. Additional file 3: of T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients

Author

Houtman, Miranda, Ekholm, Louise, Hesselberg, Espen, Chemin, Karine, Malmström, Vivianne, Reed, Ann, Lundberg, Ingrid, and Padyukov, Leonid

Abstract

Clustering heat map showing cellular heterogeneity in CD4+ and CD8+ T-cell subsets. Figure S1 shows a clustering heat map indicating cellular heterogeneity in CD4+ and CD8+ T-cell subsets, which indicates minor contamination of other cell types in these subsets. (DOCX 290 kb)

Published
2018
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9. Additional file 1: of T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients

Author

Houtman, Miranda, Ekholm, Louise, Hesselberg, Espen, Chemin, Karine, Malmström, Vivianne, Reed, Ann, Lundberg, Ingrid, and Padyukov, Leonid

Abstract

Additional clinical characteristics of patients included in this study. Tables S1–S3 provide additional clinical characteristics of patients included in this study regarding PM and DM. Table S1 includes all patients, whereas, Tables S2 and S3 contain the data for the CD4+ and CD8+ T-cell subsets, respectively. Tables S4 and S5 provide additional clinical characteristics of patients included in this study regarding HLA-DRB1*03 status. Table S4 includes all patients, whereas Table S5 contains the data for the CD4+ T-cell subset. (DOCX 24 kb)

Published
2018
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10. Additional file 6: of T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients

Author

Houtman, Miranda, Ekholm, Louise, Hesselberg, Espen, Chemin, Karine, Malmström, Vivianne, Reed, Ann, Lundberg, Ingrid, and Padyukov, Leonid

Abstract

Differentially expressed genes in CD4+ T cells of HLA-DRB1*03-positive and -negative myositis patients. Table S11 and S12 provide differentially expressed genes for CD4+ T cells of HLA-DRB1*03-positive and -negative myositis patients at analytical stage 1 (including potential outliers) and analytical stage 2 (excluding potential outliers), respectively. (DOCX 16 kb)

Published
2018
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11. Additional file 2: of T-cell transcriptomics from peripheral blood highlights differences between polymyositis and dermatomyositis patients

Author

Houtman, Miranda, Ekholm, Louise, Hesselberg, Espen, Chemin, Karine, Malmström, Vivianne, Reed, Ann, Lundberg, Ingrid, and Padyukov, Leonid

Subjects
health care economics and organizations
Abstract

Differentially expressed genes for CD4+ T cells of PM and DM patients. Table S6 and S7 provide differentially expressed genes for CD4+ T cells of PM and DM patients at analytical stage 1 (including potential outliers) and analytical stage 2 (excluding potential outliers), respectively. (DOCX 18 kb)

Published
2018
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12. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis

Author

Liu, Yun, primary, Aryee, Martin J, additional, Padyukov, Leonid, additional, Fallin, M Daniele, additional, Hesselberg, Espen, additional, Runarsson, Arni, additional, Reinius, Lovisa, additional, Acevedo, Nathalie, additional, Taub, Margaret, additional, Ronninger, Marcus, additional, Shchetynsky, Klementy, additional, Scheynius, Annika, additional, Kere, Juha, additional, Alfredsson, Lars, additional, Klareskog, Lars, additional, Ekström, Tomas J, additional, and Feinberg, Andrew P, additional

Published
2013
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