Elsevier

Hepatology

Volume 21, Issue 4, April 1995, Pages 995-1002
Hepatology

Other clinical study
T-cell responses to the components of pyruvate dehydrogenase complex in primary biliary cirrhosis

https://doi.org/10.1016/0270-9139(95)90246-5Get rights and content

Abstract

Primary biliary cirrhosis (PBC) is an autoimmune condition that results in destruction of the intrahepatic biliary epithelial cells and is characterized by autoantibodies to pyruvate dehydrogenase complex (PDC). The portal tract T-cell infiltrate and up-regulation of HLA class I, HLA class II, and cell adhesion molecules such as intercellular adhesion molecule-1 on the biliary epithelial cells suggest that T cells play a significant role in mediating this damage. The authors have characterized the peripheral blood T-cell proliferative responses of 24 PBC patients and 48 controls (20 normal, 28 non-PBC chronic liver disease) to the dominant autoantigen PDC, and its constituent components E1, E2 and protein X (which co-purify), and E3. A significant proportion of both PBC patients and controls showed T-cell responses to whole PDC (12 of 24 vs. 24 of 48 SI > 2.5 P = NS) and E1 (15 of 24 vs. 25 of 48 P = NS). Responses to PDC and El are thus seen in normal individuals and are not limited to PBC patients. T-cell responses to E2/X were seen in most PBC patients (14 of 24), but in only a small number of controls (6 of 48, P < .0001), responses to E2/X being significantly more frequent in pre-cirrhotic PBC patients (stages I to III, 12 of 15) than cirrhotic (stage IV, 2 of 9 P < .05). Peripheral blood T-cell responses to E2/X are thus strongly associated with early PBC. Responses to E3 were low in both PBC patients and controls. No differences were seen in responses to the control antigen tetanus toxoid between PBC patients and controls. These in vitro observations are compatible with the view that peripheral mechanisms may play a significant role in maintaining self-tolerance to PDC in the normal state, and that the expression of specific Tcell responses to PDC-E2/X in vivo in PBC patients may be a consequence of impairment of these mechanisms of peripheral tolerance.

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  • Cited by (0)

    DEJJ is supported by a Medical Research Council Training Fellowship. JMP is supported by the Wellcome Trust. United Kingdom, and the Northern Regional Health Authority, United Kingdom.

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