Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection
In: Clinical and Experimental Immunology, Jg. 97 (1994-07-01), S. 94-99
Online
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Zugriff:
SUMMARY LKM-1 antibody, which characterizes a subtype of autoimmune hepatitis (AIH), is also found in some patients with chronic hepatitis C virus (HCV) infection. It has been suggested that HCV initiates autoimmunity through molecular mimicry, because there is partial identity between HCV and cytochrome P4502D6 (CYP2D6), the putative target of LKM-1. Whether CYP2D6 is the target of LKM-1 in HCV-related liver disease, however, is controversial. To clarify this issue, we have studied by phage plaque assay and Western blot the reactivity to recombinant CYP2D6, isolated from a human liver cDNA library, in 55 patients with LKM-1, 18 (14 females, median age 12 years) anti-HCV-negative, with classical AIH, and 37 (27 females, median age 52 years) anti-HCV-positive. Reactivity to CYP2D6 was found in 72% of the anti-HCV-negative, but only in 27% of the anti-HCV-positive patients (P < 0.001), although immunofluorescence LKM-1 titres were similar in the two groups. In addition, to investigate whether the antibody responsible for the LKM-1 fluorescent pattern also reacts with CYP2D6, we have determined the specificity of LKM-1 antibodies present in the supernatant of lymphoblastoid B cell lines obtained from two patients with LKM-1-positive AIH. An oligo/monoclonal antibody thus generated gave both the typical fluorescent pattern and reacted with CYP2D6. Our results show that whilst antibodies producing the characteristic LKM-1 fluorescent pattern can react with CYP2D6, not all LKM-1-positive sera do so, particularly if obtained from patients with chronic HCV infection. This suggests that LKM-1 in HCV infection recognizes epitopes or antigens different from those targeted in AIH.
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Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection
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Autor/in / Beteiligte Person: | Lenzi, M. ; Lobo-Yeo, A ; Wen, Li ; Farzaneh, Farzin ; Vergani, Diego ; Peakman, Mark ; Bianchi, Francesco B. ; Ma, Yun ; Mieli-Vergani, Giorgina ; Gaken, Joop |
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Zeitschrift: | Clinical and Experimental Immunology, Jg. 97 (1994-07-01), S. 94-99 |
Veröffentlichung: | Oxford University Press (OUP), 1994 |
Medientyp: | unknown |
ISSN: | 1365-2249 (print) ; 0009-9104 (print) |
DOI: | 10.1111/j.1365-2249.1994.tb06585.x |
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