Autoimmunity may be observed in chronic viral
hepatitis, in particular
hepatitis C and D. The hepatitis C virus (HCV) displays numerous interactions with the immune system. Hepatitis C virus induces a number of diseases of presumed autoimmune background, like mixed cryoglobulinaemia,
glomerulonephritis, panarthritis,
arthritis,
thyroiditis and skin lesions. On the other hand a number of
autoantibodies are observed during the course of
hepatitis C. Of particular interest are liver/kidney microsomal
antibodies (LKM). Their occurrence in viral
hepatitis may indicate an increased risk for treatment with
interferons. LKM
antibodies in
chronic hepatitis C recognize several autoepitopes differing from those in
autoimmune hepatitis.
Hepatitis C-associated LKM
antibodies are more heterogeneous. They recognize either conformational or several distinct linear autoepitopes on
cytochrome P450 2D6; they may also react with other microsomal
proteins. Apart from their molecular weight at 59 and 70 kDa these microsomal
antigens are not yet identified. Another model of virus-induced autoimmunity in man is
chronic hepatitis D which always requires
co-infection with
hepatitis B.
Hepatitis D is known to be associated with a number of
autoantibodies, amongst them
LKM-3.
LKM-3 antibodies have recently been shown to react with
proteins of the
UDP glucuronosyltransferase family (UGT). The main
antigen is an autoepitope expressed on exon 2-5 of family 1 UGTs. Some
hepatitis D sera recognize a minor second
epitope on family 2 UGTs. It is interesting that
hepatitis C patients recognize
proteins of the
cytochrome P450 family while
hepatitis D sera react with UGTs. There seems to be little overlap between autoimmunity seen in
hepatitis C and D as far as autoepitopes are concerned.
LKM-3 antibodies against UGT 1 are also seen in a minority of patients with
autoimmune hepatitis type 2. However, the autoimmune response against UGTs seen in
autoimmune hepatitis differs from that observed in viral
hepatitis.
Autoantibodies in autoimmune
liver disease are usually more homogenous and are directed against precise linear
epitopes. Autoepitopes in
autoimmune hepatitis usually represent conserved regions of these
proteins, the antibody usually is inhibitory and antibody titres are very high. In contrast,
autoantibodies in viral
hepatitis are more heterogenous, recognize several linear and conformational
epitopes; antibody titres are much lower. However, the major LKM
autoantigen in
chronic hepatitis C also is P450 2D6.
Autoimmune hepatitis and autoimmunity in viral
hepatitis must be distinguished clinically by all means due to the need for specific therapeutic interventions. These
liver diseases may serve as models to study virus induced autoimmunity and
autoimmune disease in man.