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

✍ Scribed by David E. J. Jones; Jeremy M. Palmer; Oliver F. W. James; Stephen J. Yeaman; Margaret F. Bassendine; Austin G. Diamond

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 903 KB
• Volume: 21
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840210417

✦ Synopsis

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 11, 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 El, 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 El (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 < .Owl), responses to E2/X being significantly more frequent in pre-cirrhotic PBC patients (stages I to 111, 12 of 15) than cirrhotic (stage IV, 2 of 9 P < .05). Peripheral blood T-cell responses to E m 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 uitro 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-EYX in uivo in PBC patients may be a consequence of impairment of these mechanisms of peripheral tolerance. (HEPATOLOGY 1995;21:995-1002.