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T cell immuno-phenotyping : a source of predictive biomarkers for autoimmune hepatitis relapse

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  • Additional Information
    • Contributors:
      Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t) (Team 4 - U1064 Inserm - CR2TI); Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Centre Hospitalier Universitaire Rennes; Centre d'Investigation Clinique Rennes (CIC); Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou -Institut National de la Santé et de la Recherche Médicale (INSERM); Nutrition, Métabolismes et Cancer (NuMeCan); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Centre Hospitalier Régional Universitaire de Tours (CHRU Tours); Université d'Angers (UA); Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers La Milétrie ); Hôpital Guillaume-et-René-Laennec Saint-Herblain; Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST); GenSight Biologics; Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes); Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM); Hôpital Claude Huriez Lille; Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Université de Lille; Département de Pathologie CHU Nantes; Nantes Université (Nantes Univ); ANR-19-CE17-0024-01, Agence Nationale de la Recherche; ANR-19-CE17-0024,DISTAL,Signature lymphocytaire T auto-antigène-spécifique au cours des maladies auto-immunes du foie(2019)
    • Publication Information:
      CCSD
      Nature Publishing Group
    • Publication Date:
      2024
    • Collection:
      Institut National de la Recherche Agronomique: ProdINRA
    • Abstract:
      International audience ; Relapse after immunosuppression (IS) treatment withdrawal is frequent in patients with Autoimmune Hepatitis (AIH), and non-invasive biomarkers predictive of this risk are lacking. We assessed the frequency of circulating T cell subsets as potential biomarkers of disease activity and predictor of the risk of relapse after IS withdrawal. Serum levels of the cytokine B-cell Activating Factor (BAFF) were also investigated. Blood samples from 58 patients with active AIH, 56 AIH patients in remission, and 31 patients with NASH were analyzed. The frequency of activated CD4+ T peripheral helper (TPH) cells (CD4+CD45RA-CXCR5-PD1+CD38+) and of activated CD8+ T cells (CD8+CD45RA-PD1+CD38+) were assessed by flow cytometry. BAFF levels were determined by ELISA. Activated TPH and CD8+ T cell frequencies were significantly increased in patients with active AIH compared to remission AIH or NASH (TPH: 0.88% of total CD3+ vs. 0.42% and 0.39% respectively, p < 0.0001; CD8+ subset: 1.42% vs. 0.09% and 0.11% p < 0.0001). Among patients in remission undergoing treatment withdrawal ( n = 18), those with increased frequencies of activated TPH (> 0.5% of total CD3+) and/or activated CD8+ T cells (> 0.18% total CD3+) had a higher risk of relapse (80% vs. 15% after 2 years, p = 0.0071). High BAFF serum concentration (> 213pg/ml) was also associated to a higher risk of relapse (57% vs. 11%, p = 0.0452). In conclusion, high frequency of activated TPH and of activated CD8+, as well as high levels of BAFF, before IS discontinuation, were significantly associated to a greater risk of relapse during the first two years. Thus, they represent promising biomarkers to provide personalized clinical follow-up for patients with AIH.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/39424872; PUBMED: 39424872; PUBMEDCENTRAL: PMC11489469
    • Accession Number:
      10.1038/s41598-024-75624-6
    • Online Access:
      https://inserm.hal.science/inserm-04810501
      https://inserm.hal.science/inserm-04810501v1/document
      https://inserm.hal.science/inserm-04810501v1/file/s41598-024-75624-6.pdf
      https://doi.org/10.1038/s41598-024-75624-6
    • Rights:
      info:eu-repo/semantics/OpenAccess
    • Accession Number:
      edsbas.F3DE9909