Toggle Main Menu Toggle Search

Open Access padlockePrints

Oral tolerisation to pyruvate dehydrogenase complex as a potential therapy for primary biliary cirrhosis

Lookup NU author(s): Professor David Jones, Dr Jeremy Palmer, Dr Amanda Robe, Professor John Kirby

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Primary biliary cirrhosis (PBC) is characterised by immune-mediated damage to the intra-hepatic biliary epithelial cells (BEC). Immuno-modulatory/suppressive therapy represents, therefore, a logical approach to treatment in this disease. Conventional immuno-suppressive and immuno-modulatory agents suffer from the breadth of their action and/or excessive side effects. Autoreactive responses to pyruvate dehydrogenase complex (PDC) have been extensively characterised in PBC, and implicated in target cell damage. The aim of the current study was to study the potential efficacy of an antigen specific approach (oral tolerisation with autoantigen) to modulation of anti-PDC immune responses characteristic of PBC, utilising a mouse model of PDC immuno-reactivity. Groups of SJL/J mice were orally dosed with PDC alone, dosed with carrier only (saline) but systemically sensitised with PDC in adjuvant, or orally dosed with PDC at high (5 mg) or low (0.01 mg) dose and systemically sensitised with PDC. Oral dosing with PDC in isolation had no adverse effects on the animals and did not prime anti-PDC responses at doses below 1 mg. Pre-dosing with PDC at both high and low doses was effective at skewing the phenotype of the T-cell response to PDC induced by subsequent sensitisation away from the disease associated Th-1 phenotype (IL-2 and IFN-γ secreting) and towards a theoretically protective Th-2 phenotype (IL-4 secreting) in a majority of, but not all, animals. No augmentation of Th-1 response was seen in any animal. Although the effects on liver histology remain to established oral tolerisation with PDC holds promise as a novel, antigen specific approach to therapy in PBC.


Publication metadata

Author(s): Jones DEJ, Palmer JM, Robe A, Kirby JA

Publication type: Article

Publication status: Published

Journal: Autoimmunity

Year: 2002

Volume: 35

Issue: 8

Pages: 537-544

Print publication date: 01/12/2002

ISSN (print): 0891-6934

ISSN (electronic): 1026-7859

Publisher: Informa Healthcare

URL: http://dx.doi.org/10.1080/0891693021000054084

DOI: 10.1080/0891693021000054084

PubMed id: 12765480


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share