Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis
Background & Aims: In patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555921000598 |
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| author | Shvetank Sharma Sukriti Baweja Jaswinder S. Maras Saggere M. Shasthry Richard Moreau Shiv K. Sarin |
| author_facet | Shvetank Sharma Sukriti Baweja Jaswinder S. Maras Saggere M. Shasthry Richard Moreau Shiv K. Sarin |
| author_sort | Shvetank Sharma |
| collection | DOAJ |
| description | Background & Aims: In patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who cannot (steroid-non-responders [NR]); 2 groups with different outcomes. Methods: We performed RNA-seq analysis in PBMCs from 32 patients with definite SAH, at baseline and after 7 days of corticosteroids. The data were sorted into R and NR (n = 16, each group) using the Lille model and 346 blood transcription modules (BTMs) were identified. BTMs are predefined modules of highly co-expressed PBMC genes, which can determine specific immune cell types and cellular functions. The activity of each BTM was taken as the mean value of its member genes. Results: At baseline, 345 BTMs had higher activity (i.e. were upregulated) in NR relative to R. The 100 most upregulated BTMs in NR, included several modules related to lymphoid lineage (T, B, and natural killer [NK] cells), modules for cell division and mitochondrial respiratory electron transport chain (ETC, relating to energy production), but only a few modules of myeloid cells. Correlation studies of BTM activities found features of significantly greater activation/proliferation and differentiation for T and B cells in NR relative to R. After 7 days of corticosteroids, NR had no significant changes in BTM activities relative to baseline, whereas R had downregulation of BTMs related to innate and adaptive immunity. Conclusions: At baseline and during corticosteroid therapy, increased activity in the PBMCs of gene modules related to activation/proliferation and differentiation of T and B cells, NK cells, and mitochondrial ETC, is a hallmark of SAH patients who are steroid-non-responders. Lay summary: Patients with severe alcoholic hepatitis receive steroid therapy as the main line of treatment; however, this treatment is ineffective in some patients. This only becomes apparent after 7 days of steroid therapy. We have developed an approach where it can be estimated if a patient is going to respond or not to steroid therapy using the gene expression information of blood cells. This method will allow clinicians to assess the response of patients to steroids earlier, and will help them in adopting alternate strategies if the treatment is found to be ineffective in a particular patient. |
| first_indexed | 2024-04-11T20:19:31Z |
| format | Article |
| id | doaj.art-90c9aa3e032f4e25a733d0dca5e151dd |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-04-11T20:19:31Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-90c9aa3e032f4e25a733d0dca5e151dd2022-12-22T04:04:52ZengElsevierJHEP Reports2589-55592021-06-0133100283Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitisShvetank Sharma0Sukriti Baweja1Jaswinder S. Maras2Saggere M. Shasthry3Richard Moreau4Shiv K. Sarin5Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, IndiaDepartment of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, IndiaDepartment of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, IndiaDepartment of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, IndiaCentre de Recherche sur l’Inflammation (CRI), INSERM, Université de Paris, Paris, France; Service d’Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, FranceDepartment of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India; Corresponding author. Address: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110070, India. Tel.: +91 11 46 300 000; fax: +91 11 26 123 504.Background & Aims: In patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who cannot (steroid-non-responders [NR]); 2 groups with different outcomes. Methods: We performed RNA-seq analysis in PBMCs from 32 patients with definite SAH, at baseline and after 7 days of corticosteroids. The data were sorted into R and NR (n = 16, each group) using the Lille model and 346 blood transcription modules (BTMs) were identified. BTMs are predefined modules of highly co-expressed PBMC genes, which can determine specific immune cell types and cellular functions. The activity of each BTM was taken as the mean value of its member genes. Results: At baseline, 345 BTMs had higher activity (i.e. were upregulated) in NR relative to R. The 100 most upregulated BTMs in NR, included several modules related to lymphoid lineage (T, B, and natural killer [NK] cells), modules for cell division and mitochondrial respiratory electron transport chain (ETC, relating to energy production), but only a few modules of myeloid cells. Correlation studies of BTM activities found features of significantly greater activation/proliferation and differentiation for T and B cells in NR relative to R. After 7 days of corticosteroids, NR had no significant changes in BTM activities relative to baseline, whereas R had downregulation of BTMs related to innate and adaptive immunity. Conclusions: At baseline and during corticosteroid therapy, increased activity in the PBMCs of gene modules related to activation/proliferation and differentiation of T and B cells, NK cells, and mitochondrial ETC, is a hallmark of SAH patients who are steroid-non-responders. Lay summary: Patients with severe alcoholic hepatitis receive steroid therapy as the main line of treatment; however, this treatment is ineffective in some patients. This only becomes apparent after 7 days of steroid therapy. We have developed an approach where it can be estimated if a patient is going to respond or not to steroid therapy using the gene expression information of blood cells. This method will allow clinicians to assess the response of patients to steroids earlier, and will help them in adopting alternate strategies if the treatment is found to be ineffective in a particular patient.http://www.sciencedirect.com/science/article/pii/S2589555921000598Alcoholic liver diseaseTranscriptomeSteroidGlucocorticoid receptorNR3C1 |
| spellingShingle | Shvetank Sharma Sukriti Baweja Jaswinder S. Maras Saggere M. Shasthry Richard Moreau Shiv K. Sarin Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis JHEP Reports Alcoholic liver disease Transcriptome Steroid Glucocorticoid receptor NR3C1 |
| title | Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis |
| title_full | Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis |
| title_fullStr | Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis |
| title_full_unstemmed | Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis |
| title_short | Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis |
| title_sort | differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis |
| topic | Alcoholic liver disease Transcriptome Steroid Glucocorticoid receptor NR3C1 |
| url | http://www.sciencedirect.com/science/article/pii/S2589555921000598 |
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