1. 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
- Author
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Giorgina Mieli-Vergani, Dimitrios P. Bogdanos, Paolo Muratori, Francesco B. Bianchi, D. Tsantoulas, Diego Vergani, Luigi Muratori, Eirini I. Rigopoulou, M. Lenzi, M. Okamoto, Yun Ma, D.P. BOGDANOS, M. LENZI, M. OKAMOTO M, E.I. RIGOPOULOU, P. MURATORI, Y. MA, L. MURATORI, D. TSANTOULAS, G. MIELI- VERGANI, F.B. BIANCHI, and D. VERGANI
- Subjects
Adult ,Male ,CHRONIC/*IMMUNOLOGY ,Genotype ,viruses ,Hepatitis C virus ,Hepacivirus ,Immunology ,Molecular Sequence Data ,CYTOCHROME P-450 CYP2D6/BLOOD/GENETICS ,Autoimmune hepatitis ,Cross Reactions ,medicine.disease_cause ,Kidney ,Cross-reactivity ,Virus ,03 medical and health sciences ,0302 clinical medicine ,medicine ,AUTOANTIBODIES/*METABOLISM ,Immunology and Allergy ,Humans ,Amino Acid Sequence ,Aged ,Autoantibodies ,Pharmacology ,biology ,Histocompatibility Testing ,Autoantibody ,Hepatitis C Antibodies ,Hepatitis C, Chronic ,Middle Aged ,biology.organism_classification ,medicine.disease ,Virology ,Peptide Fragments ,Molecular mimicry ,Herpes simplex virus ,Cytochrome P-450 CYP2D6 ,HLA-B Antigens ,030220 oncology & carcinogenesis ,HEPATITIS C ,HLA-B51 Antigen ,Microsomes, Liver ,Female ,Binding Sites, Antibody ,030215 immunology - Abstract
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.
- Published
- 2004