Pediatric autoimmune hepatitis shows a disproportionate decline of regulatory T cells in the liver and of IL-2 in the blood of patients undergoing therapy.

PLoS One 2017 11;12(7):e0181107. Epub 2017 Jul 11.

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Background & Aims: The autoimmune hepatitis (AIH) is a chronic hepatitis driven by the adaptive immunity that affects all age groups. A functional and numerical regulatory T cell (Treg) defect has been reported in pediatric AIH (pAIH), while an intrahepatic increase in adult AIH (aAIH) patients has been detected in current research findings.

Methods: Therefore, we quantified the intrahepatic numbers of Treg, T and B cells, as well as serum cytokine levels before and during therapy in pAIH.

Results: We found a disproportional intrahepatic enrichment of Tregs in untreated pAIH compared to pediatric non-alcoholic fatty liver disease. The increase of Treg/total T cells was even more pronounced than in aAIH due to fewer infiltrating T and B cells. Portal densities of Treg, as well as total T and B cells, declined significantly during therapy. However, portal Treg densities decreased disproportionately, leading to even decreasing ratios of Treg to T and B cells during therapy. Out of 28 serum cytokines IL-2 showed the strongest (10fold) decrease under therapy. This decline of IL-2 was associated with decreasing intrahepatic Treg numbers under therapy. None of the baseline T and B cell infiltration parameters were associated with the subsequent treatment response in pAIH.

Conclusions: Intrahepatic Tregs are rather enriched in untreated pAIH. The disproportional decrease of Tregs during therapy may be caused by a decrease of IL-2 levels. New therapies should, therefore, aim in strengthening intrahepatic immune regulation.

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181107PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507441PMC
September 2017
54 Reads

Publication Analysis

Top Keywords

treg cells
8
untreated paih
8
autoimmune hepatitis
8
therapy
7
cells
6
treg
6
intrahepatic
6
total cells
4
cells declined
4
well total
4
treg well
4
cells portal
4
portal densities
4
densities treg
4
declined therapy
4
portal treg
4
leading decreasing
4
decreasing ratios
4
ratios treg
4
disproportionately leading
4

Similar Publications