T-cell responses to the components of pyruvate dehydrogenase complex in primary biliary cirrhosis.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Jones
D E
DE
Department of Medicine, University of Newcastle, England.
Palmer
J M
JM
James
O F
OF
Yeaman
S J
SJ
Bassendine
M F
MF
Diamond
A G
AG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D007074:Immunoglobulin G; C045867:PDHX protein, human; D010455:Peptides; D011768:Pyruvate Dehydrogenase Complex; D013745:Tetanus Toxoid; D051047:Dihydrolipoyllysine-Residue Acetyltransferase