Value of autoantibody analysis in the differential diagnosis of chronic cholestatic liver disease.
OBJECTIVE
It is challenging to diagnose patients with chronic cholestatic liver diseases when all the classic criteria are not fulfilled. We evaluated the performance of the recently developed MIT3-based enzyme-linked immunosorbent assay (ELISA), which detects antimitochondrial autoantibodies (AMAs), together with ELISAs for other autoimmune liver disease-related antibodies in patients with chronic cholestatic liver disease.


METHODS
Sera from 281 patients with chronic cholestatic conditions, including primary biliary cirrhosis (PBC), primary sclerosing cholangitis, AMA-positive autoimmune hepatitis, and "undetermined cholangiopathy" were tested for the following PBC-associated autoantibodies: anti-gp210, anti-sp100, conventional anti-M2, anti-M2 (MIT3) IgG, anti-M2 (MIT3) IgA, as well as anti-centromere, anti-soluble liver antigen, and anti-chromatin.


RESULTS
Of 57 patients with PBC who were AMA-negative by conventional M2 ELISA, 14 were found to be AMA-positive by the MIT3-IgG assay. Furthermore, on the basis of the data from 3 tests (MIT3-IgG, gp210, and sp100), PBC was confirmed in 20 of 57 (35%) patients diagnosed with AMA-negative PBC. We confirmed that sp100 and gp210 antibodies were detected only in patients with PBC and AMA-positive autoimmune hepatitis, whereas gp210 was detected more frequently in patients known to have had a poor outcome. Of the 11 patients with an undetermined cholangiopathy, 3 (27%) tested positive for PBC with the MIT3-IgG assay. In contrast to previous findings, anti-centromere antibodies were not found to be associated with poor outcome in PBC.


CONCLUSIONS
ELISAs for AMAs and antinuclear antibodies are useful in diagnosis and prognosis of patients with features of PBC who lack conventional AMA and in patients with a cholangiopathy of undetermined etiology.
Milkiewicz
Piotr
P
Department of Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Buwaneswaran
Hayman
H
Coltescu
Catalina
C
Shums
Zakera
Z
Norman
Gary L
GL
Heathcote
E Jenny
EJ
D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000175:diagnosis*; D002779:Cholestasis / Q000150:complications*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000276:immunology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D024101:Mitochondrial Proteins