Premium
T‐cell responses to the components of pyruvate dehydrogenase complex in primary biliary cirrhosis
Author(s) -
Jones David E. J.,
Palmer Jeremy M.,
James Oliver F. W.,
Yeaman Stephen J.,
Bassendine Margaret F.,
Diamond Austin G.
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840210417
Subject(s) - primary biliary cirrhosis , autoantibody , biliary cirrhosis , medicine , biliary tract , immunology , lactate dehydrogenase , autoimmunity , cell adhesion molecule , autoimmune disease , endocrinology , gastroenterology , immune system , biology , antibody , disease , enzyme , biochemistry
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 E1 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 T‐cell responses to PDC‐E2/X in vivo in PBC patients may be a consequence of impairment of these mechanisms of peripheral tolerance. (H EPATOLOGY 1995; 21:995–1002.)