LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase.
LKM-1 autoantibodies, which are associated with autoimmune chronic active hepatitis, recognize P450IID6, a cytochrome P-450 monooxygenase. The reactivities of 26 LKM-1 antisera were tested with a panel of deletion mutants of P450IID6 expressed in Escherichia coli. 22 sera recognize a 33-amino acid segment of P450IID6, and 11 of these recognize a shorter segment, DPAQPPRD. PAQPPR is also found in IE175 of herpes simplex virus type 1 (HSV-1). Antibodies for HSV-1 proteins were detected by ELISA in 17 of 20 LKM-1 sera tested. An immobilized, synthetic peptide, DPAQPPRDC, was used to purify LKM-1 antibodies. Affinity purified LKM-1 autoantibodies react on immunoblots with a protein in BHK cells after infection with HSV-1. 11 of 24 LKM-1 sera, including 3 that recognize DPAQPPRD, also exhibit antibodies to the hepatitis C virus (HCV) protein, C100-3. Affinity purified LKM-1 antibodies did not recognize C100-3. However, partial sequence identity was evident between portions of the immunopositive 33-amino acid segment of P450IID6 and other portions of the putative HCV polyprotein. Immune cross-recognition of P450IID6 and HCV or HSV-1 proteins may contribute to the occurrence of LKM-1 autoantibodies.
Manns
M P
MP
Department of Medicine I, University of Mainz, Federal Republic of Germany.
Griffin
K J
KJ
Sullivan
K F
KF
Johnson
E F
EF
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D006521:Hepatitis, Chronic / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010105:Oxygenases / Q000032:analysis / Q000276:immunology*; D018139:Simplexvirus / Q000276:immunology; D014764:Viral Proteins / Q000032:analysis / Q000276:immunology
D000914:Antibodies, Viral; D001323:Autoantibodies; D000939:Epitopes; D014764:Viral Proteins; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases