Detection of IgA, IgM, and IgG subclasses of anti-M2 antibody by immunoblotting in autoimmune cholangitis: is autoimmune cholangitis an early stage of primary biliary cirrhosis?
Autoimmune cholangitis (AIC) has been proposed as a distinct disease entity from primary biliary cirrhosis (PBC), without antimitochondrial antibody (AMA) and anti-M2 antibody but with a high titer of antinuclear antibody (ANA) in the serum. However, negativity for AMA and anti-M2 antibody was determined by different methods in different studies. We hypothesized that anti-M2 antibody negativity in AIC resulted from methodological differences, including selection of the immunoglobulin subclass of the autoantibody. Twenty-three patients compatible with AIC whose serum tested negative for AMA and positive for ANA (> or = 1:80) were compared with 71 AMA-positive PBC patients. Laboratory findings, histology, and the pattern of anti-M2 antibody assessed by immunoblotting were compared. Alkaline phosphatase, total bilirubin, total cholesterol, and IgM values were lower in patients with AIC (P < 0.05, 0.01, respectively). Anti-smooth muscle antibody was detected more frequently in patients with AIC (P < 0.01). However, anti-M2 antibody was detected using immunoblotting not only in PBC but also in AIC cases. IgA class alone, IgM class alone, or both IgA and IgM classes of anti-M2 antibody were detected in 13%, 17%, and 22% of AIC patients, respectively, whereas they were not detected in PBC patients (P < 0.05, P < 0.01, P < 0.01). IgG class anti-M2 was detected in all patients with PBC, whereas it was detected in 48% of patients with AIC (P < 0.01). Histological evaluation showed that the early stages of disease were found more frequently in AIC (78%) than in PBC patients (39%) (P < 0.01). Anti-M2 antibody was detected by immunoblotting in all AIC patients. Hence, AIC is not a distinct disease from PBC. For diagnosing AIC and/or PBC, anti-M2 antibody should be examined by the immunoblotting assay to detect not only IgG but also IgA and IgM subclasses.
Nakajima
M
M
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
Shimizu
H
H
Miyazaki
A
A
Watanabe
S
S
Kitami
N
N
Sato
N
N
D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D002761:Cholangitis / Q000276:immunology*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000276:immunology*; D008105:Liver Cirrhosis, Biliary / Q000209:etiology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology; D018709:Statistics, Nonparametric
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins