Spatial analysis of the inflammation in spontaneous and immunotherapy-related autoimmune hepatitis
Immune-Checkpoint-Blockade associated Hepatitis (ICB-Hepatitis) develops under Immune-Checkpoint-Inhibition and poses a serious challenge in clinical management. In contrast, Autoimmune Hepatitis (AIH) occurs spontaneously. In this study, we analyzed the spatial interaction and detailed composition of immune cells in both diseases. For this, we used a 40-marker Imaging mass cytometry (IMC) panel on ICB-Hepatitis- (n=15), AIH- (n=22) and control-samples (n=10). Normalization of samples was performed by a machine-learning approach.
Our clustering approach showed an enrichment of B cells, CD4+ T cells and exhausted CD8+ T cells in AIH. Furthermore, a significant fraction of CD8+ cells exhibited a tissue resident memory (Trm) phenotype. Interestingly, this Trm cluster correlated with clinical parameters in AIH. The spatial analysis pointed to an interaction of Trm cells with exhausted T cells and myeloid clusters. Clustering of cells into distinct tissue regions of the liver revealed a unique zonal distribution in AIH. Specifically, B cells and CD4+ T cells located to the periportal triad.
In sum, IMC enabled us to identify striking differences in the composition and spatial interactions of immune cells between ICB-Hepatitis and AIH.
Laurenz Krimmel is a medical student and currently performing his doctoral thesis at the Clinic for Internal Medicine II at the University Medical Center Freiburg in the group of Prof. Bengsch.
Clinic for Internal Medicine II, University Medical Center Freiburg, Freiburg, Germany