Multiple viral/self immunological cross-reactivity in liver kidney microsomal antibody positive hepatitis C virus infected patients is associated with the possession of HLA B51.
Liver Kidney Microsomal autoantibody type 1(LKM1) directed to cytochrome P4502D6 (CYP2D6) characterises autoimmune hepatitis type-2 (AIH-2), but is also found in a proportion of chronic hepatitis C virus (HCV) infected patients, CYP2D6252-271 being a major B- cell autoepitope. Molecular mimicry and immunological cross-reactivity between CYP2D6252-271, HCV polyprotein and the infected cell protein 4 (ICP4) of herpes simplex virus type 1 (HSV-1) have been suggested as triggers for the induction of LKM1, but reactivity and cross-reactivity to the relevant sequences have not been investigated experimentally. CYP2D6252-271 and its viral homologues were constructed and tested by ELISA in the sera of 46 chronically infected HCV patients, 23 of whom were LKM1 positive. Reactivity to the E1 HCV and ICP4 HSV1 mimics was frequently found in HCV infected patients irrespectively of their LKM1 status; viral/self cross-reactivity (as indicated by inhibition studies), however, was present in the only 2 of the 23 LKM1 seropositive HCV patients, who possessed the HLA allotype B51. Our results indicate that in HCV infected patients virus/self cross-reactivity is dependent on a specific immunogenetic background, a finding awaiting confirmation by studies in larger series of patients.
Immunology, Institute of Liver Studies, King's College Hospital, London, UK.
D-P
DP
Bogdanos
M
M
Lenzi
M
M
Okamoto
E I
EI
Rigopoulou
P
P
Muratori
Y
Y
Ma
L
L
Muratori
D
D
Tsantoulas
G
G
Mieli- Vergani
F B
FB
Bianchi
D
D
Vergani
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000378:metabolism*; D001666:Binding Sites, Antibody; D003429:Cross Reactions; D019389:Cytochrome P-450 CYP2D6 / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D015235:HLA-B Antigens / Q000378:metabolism*; D059949:HLA-B51 Antigen; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007668:Kidney / Q000276:immunology*; D008297:Male; D008862:Microsomes, Liver / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; D018937:Hepatitis C Antibodies; D010446:Peptide Fragments; C060729:anti-liver kidney microsome antibody; D019389:Cytochrome P-450 CYP2D6