studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 511A
cholangitis (ASC) – and 16 healthy subjects (HS) were studied.
Peripheral blood cell phenotype was determined by flow
cytometry; ability to suppress was evaluated as inhibition of
cell proliferation/effector cytokine production; ectoenzymatic
activity by thin layer chromatography; expression of adenosine
receptor, adenosine deaminase (ADA) and phosphodiesterases
(PDE) by quantitative real-time PCR or Western Blot.
Results: As compared to their CD39 - counterpart, Th17 CD39+
cells retained expression of CCR6, IL-23R and RORC, classical
Th17 cell markers; displayed higher frequencies of CD69 + ,
CD44 + and CD25 + activated cells; contained higher numbers
of CD73 + , CD161 + and FOXP3 + lymphocytes; and were more
frequently positive for IL-22, IL-10 and TGF-b producing cells.
The proportion of Th17 CD39+ cells was markedly lower in AILD
than HS, with ASC displaying lower proportions than AIH
patients. In AILD, Th17 CD39+ numbers are greatly decreased
and have impaired ability to generate AMP/adenosine and
to control both target cell proliferation and IL-17 production.
When compared to HS, Th17 cells from AILD patients had a
markedly decreased expression of A2A adenosine receptor
while displaying similar expression levels of PDE4A, PDE4B
and ADA. Conclusions: In AILD, Th17 CD39+ cells are numerically
decreased and defective in their ability to generate adenosine
and exert suppression. Failure of these Th17 cells to upregulate
CD39 appears linked to reduced A2A adenosine receptor levels.
Low CD39 and A2A expression may contribute, at least
in part, to the perpetuation of Th17 effector potential in AILD.
Disclosures:
Simon C. Robson - Grant/Research Support: Pfizer, NIH, Dainippon; Independent
Contractor: Biolegend, EMD Millipore, Mersana; Management Position:
eBioscience; Speaking and Teaching: ACP, Elsevier, ATC; Stock Shareholder:
Nanopharma, Puretech
The following authors have nothing to disclose: Rodrigo Liberal, Charlotte R.
Grant, Yun Ma, Michael A. Heneghan, Giorgina Mieli-Vergani, Diego Vergani,
Maria Serena Longhi
OCA on the markers of cholestasis and safety. Study inclusion
criteria: PBC diagnosis, ALP ≥1.67x ULN and/or total bilirubin
>ULN to