High prevalence of antibodies to calreticulin of the IgA class in primary biliary cirrhosis: a possible role of gut-derived bacterial antigens in itsaetiology?
W. Kreisel et al., High prevalence of antibodies to calreticulin of the IgA class in primary biliary cirrhosis: a possible role of gut-derived bacterial antigens in itsaetiology?, SC J GASTR, 34(6), 1999, pp. 623-628
Background: In a preliminary study we showed that antibodies to the endopla
smic reticulum protein calreticulin (CR) occur in primary biliary cirrhosis
(PBC) and autoimmune hepatitis type 1 (AM). Since anti-CR antibodies have
also been found in patients with infectious diseases, we investigated their
prevalence and immunoglobulin classes in patients with Various hepatic and
intestinal diseases, hoping to get some information on a possible relation
ship between an infectious trigger and the induction of a certain class of
anti-CR antibodies. Methods: Sera were tested for anti-CR antibodies of the
IgA, IgG, and IgM class by Western blotting, using CR isolated from human
liver: in autoimmune liver diseases (primary biliary cirrhosis (PBC) (n = 8
6) and autoimmune hepatitis (AIH) type 1 (n = 57)), alcoholic liver cirrhos
is (ALC) (n = 32), viral Liver infections (acute hepatitis A (n = 8), acute
hepatitis B (n = 20), and chronic hepatitis C (n = 28)), and intestinal di
seases (Crohn disease (CD) (n = 30), acute yersiniosis (n = 26)). Sera from
100 healthy individuals served as negative controls. Results: The most pro
minent finding was the high prevalence of anti-CR antibodies of the IgA cla
ss and the similarity in the anti-CR antibody class pattern in PBC (IgA, 62
%; IgG, 43%; IgM, 55%) and yersiniosis (IgA, 62%; IgG, 39%; IgM, 42%). Clas
s IgA anti-CR antibodies also occurred frequently in ALC (IgA, 44%; IgG, 41
%; IgM, 19%). In contrast, in AIH anti-CR antibodies were predominantly of
class IgG (IgA, 28%; IgG, 60%; IgM, 33%). In hepatitis A anti-CR antibodies
were absent. In the other diseases they had a low prevalence and were most
ly of class IgG (acute hepatitis B: IgA, 0%; IgG, 15%; IgM, 0%; chronic hep
atitis C: IgA, 7%; IgG, 21%; IgM, 0%; CD: IgA, 13%; IgG, 20%; IgM, 13%). Of
the healthy individuals 7% had anti-CR antibodies exclusively of class IgG
. Conclusions: The high prevalence of anti-CR antibodies of class IgA in pa
tients with PBC and yersiniosis as well as in alcoholic liver disease refle
cts a reactivity of the gut-associated immune system and could imply that a
still undefined gut-derived bacterial (?) agent may trigger PBC.