Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment
Autoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from th...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2018-08-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1202 |
| _version_ | 1797936536708186112 |
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| author | Amédée Renand Sarah Habes Jean‐François Mosnier Hélène Aublé Jean‐Paul Judor Nicolas Vince Philippe Hulin Steven Nedellec Sylvie Métairie Isabelle Archambeaud Sophie Brouard Jérôme Gournay Sophie Conchon |
| author_facet | Amédée Renand Sarah Habes Jean‐François Mosnier Hélène Aublé Jean‐Paul Judor Nicolas Vince Philippe Hulin Steven Nedellec Sylvie Métairie Isabelle Archambeaud Sophie Brouard Jérôme Gournay Sophie Conchon |
| author_sort | Amédée Renand |
| collection | DOAJ |
| description | Autoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new‐onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis. Four blood lymphocyte populations were significantly altered in AIHn patients at diagnosis compared with healthy subjects. Levels of mucosal‐associated invariant T cells (MAIT), Type 1/Type 17 helper (Th1/ Th17) cells, clusters of differentiation (CD4) T cells, and invariant natural killer T cells were decreased, whereas MAIT granzyme B+ (GrB) cells were increased. A trend toward an increase of CD8+CD161+GrB+ cells was also observed. These alterations were not restored with standard immunosuppressive treatments. In the liver of AIHn patients, CD4, forkhead box P3 (Foxp3), and MAIT cell markers were enriched in the portal tract, and CD8, CD161, and GrB markers were enriched in the hepatic lobule. During remission, the hepatic lobule was clear of infiltrating T cells, but residual CD4 and MAIT cells were found in the portal tract, where Foxp3 was decreased, as previously described. In vitro, MAIT cells were functionally altered in AIH patients. Ex vivo MAIT cell activity (GrB) was linked to severe fibrosis. Conclusion: Our work proposes a global view of the lymphocyte alterations from diagnosis to remission phase in AIH patients. The absence of blood immune homeostasis restoration and the persistence of a CD4 infiltrate in the liver under standard immunosuppression could form the basis of the high risk of relapse observed in AIH. (Hepatology Communications 2018; 00:000‐000) |
| first_indexed | 2024-04-10T18:31:07Z |
| format | Article |
| id | doaj.art-907f77c222954d06b8db5354f2a44e88 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T18:31:07Z |
| publishDate | 2018-08-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-907f77c222954d06b8db5354f2a44e882023-02-02T04:02:06ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2018-08-012897298510.1002/hep4.1202Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive TreatmentAmédée Renand0Sarah Habes1Jean‐François Mosnier2Hélène Aublé3Jean‐Paul Judor4Nicolas Vince5Philippe Hulin6Steven Nedellec7Sylvie Métairie8Isabelle Archambeaud9Sophie Brouard10Jérôme Gournay11Sophie Conchon12Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM Université de Nantes Nantes FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM Université de Nantes Nantes FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM Université de Nantes Nantes FranceCentre d'Investigation Clinique gastro‐nutrition CHU Nantes Nantes FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM Université de Nantes Nantes FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM Université de Nantes Nantes FranceMicroPICell Imaging Core Facility, SFR Santé F. Bonamy UMS016, INSERM, CNRS Université de Nantes Nantes FranceMicroPICell Imaging Core Facility, SFR Santé F. Bonamy UMS016, INSERM, CNRS Université de Nantes Nantes FranceService Chirurgie Digestive et Endocrinienne CHU Nantes Nantes FranceService Hépato‐Gastro‐entérologie et Assistance Nutritionnelle CHU Nantes Nantes FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM Université de Nantes Nantes FranceService Hépato‐Gastro‐entérologie et Assistance Nutritionnelle CHU Nantes Nantes FranceCentre de Recherche en Transplantation et Immunologie UMR1064, INSERM Université de Nantes Nantes FranceAutoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new‐onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis. Four blood lymphocyte populations were significantly altered in AIHn patients at diagnosis compared with healthy subjects. Levels of mucosal‐associated invariant T cells (MAIT), Type 1/Type 17 helper (Th1/ Th17) cells, clusters of differentiation (CD4) T cells, and invariant natural killer T cells were decreased, whereas MAIT granzyme B+ (GrB) cells were increased. A trend toward an increase of CD8+CD161+GrB+ cells was also observed. These alterations were not restored with standard immunosuppressive treatments. In the liver of AIHn patients, CD4, forkhead box P3 (Foxp3), and MAIT cell markers were enriched in the portal tract, and CD8, CD161, and GrB markers were enriched in the hepatic lobule. During remission, the hepatic lobule was clear of infiltrating T cells, but residual CD4 and MAIT cells were found in the portal tract, where Foxp3 was decreased, as previously described. In vitro, MAIT cells were functionally altered in AIH patients. Ex vivo MAIT cell activity (GrB) was linked to severe fibrosis. Conclusion: Our work proposes a global view of the lymphocyte alterations from diagnosis to remission phase in AIH patients. The absence of blood immune homeostasis restoration and the persistence of a CD4 infiltrate in the liver under standard immunosuppression could form the basis of the high risk of relapse observed in AIH. (Hepatology Communications 2018; 00:000‐000)https://doi.org/10.1002/hep4.1202 |
| spellingShingle | Amédée Renand Sarah Habes Jean‐François Mosnier Hélène Aublé Jean‐Paul Judor Nicolas Vince Philippe Hulin Steven Nedellec Sylvie Métairie Isabelle Archambeaud Sophie Brouard Jérôme Gournay Sophie Conchon Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment Hepatology Communications |
| title | Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment |
| title_full | Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment |
| title_fullStr | Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment |
| title_full_unstemmed | Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment |
| title_short | Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment |
| title_sort | immune alterations in patients with type 1 autoimmune hepatitis persist upon standard immunosuppressive treatment |
| url | https://doi.org/10.1002/hep4.1202 |
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