Hepatitis C virus-related chronic liver disease with autoantibodies to liver-kidney microsomes (LKM)

Todros, L.; Touscoz, Giovanni Antonio; D'Urso, N; Durazzo, Marilena; Albano, Emanuele; Poli, Giancarla; Baldi, M.; Rizzetto, Mario

doi:10.1016/0168-8278(91)90874-b

Cited by 85 publications

(29 citation statements)

References 10 publications

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“…Different types of organ-and non-organ-specific autoantibodies have been detected in sera from patients with chronic hepatitis C infection, without any clear relationship with the level of disease activity [14,25,26]. LKM1 are among the autoantibodies found in sera from HCV-infected patients [5,10] and are directed against a variety of microsomal proteins of rat and human liver [10][11][12][13][14]. The most constant microsomal antigens were the cytochrome P450s from the 2D subfamily [10,12,13].…”

Section: Discussionmentioning

confidence: 99%

Study of the B cell response to cytochrome P450IID6 in sera from chronic hepatitis C patients

Parez

Herzog

Jacqz-Aigrain

et al. 1996

Clinical and Experimental Immunology

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SUMMARYSome patients with chronic hepatitis C develop liver/kidney microsome type 1 antibodies. Some of these autoantibodies are directed against the cytochrome P450IID6. The aim of this study was to characterize the immunogenic sites on the P450IID6 molecule recognized by autoantibodies from individuals infected with the hepatitis C virus. Serum from 24 patients with markers of hepatitis C infection and liver/kidney microsome type 1 antibodies were tested by immunoblotting with human liver microsomal proteins. Eight of them with anti-P450IID6 antibodies were tested with synthetic peptides representing P450IID6 putative immunogenic sites and for their capacity to inhibit in vitro P450IID6 enzymatic activity. Anti-P450IID6 antibodies in the sera of chronic hepatitis C patients were of IgG subclass 1 and in one patient also of IgM type. These sera recognized different P450IID6 peptide sequences consisting of amino acids (aa) 200-214 and aa 271-339. The synthetic peptide between aa 321 and 339 appears to represent the main antigenic site. Five out of eight anti-P450IID6 positive sera were also able to inhibit P450IID6 enzymatic activity in vitro at a dilution of 1 : 100. The anti-P450IID6 autoimmune response in chronic hepatitis C patients is polyclonal, probably inducible, and maintained by the liberation of P450IID6 by hepatocyte lysis. The characterization of the P450IID6 immunogenic site recognized by patients with hepatitis C infection may enable a specific test to be designed to identify those patients with autoimmune hepatitis type 2.

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Section: Discussionmentioning

confidence: 99%

Study of the B cell response to cytochrome P450IID6 in sera from chronic hepatitis C patients

Parez

Herzog

Jacqz-Aigrain

et al. 1996

Clinical and Experimental Immunology

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“…Limited reports have indicated that these patients fail to improve with corticosteroids but they do respond to treatment with recombinant inter feron [12, 13. 20, 22], Patients with true HCV infection and anti-LKM1, regardless of titer, should also be treated initially with interferon [20], The anti bodies associated with this condition lack the epitope specificity that characterizes the au toantibodies of tvpe-2 autoimmune hepatitis [48,49], They are probably cross-reacting an tibodies that do not have a diagnostic conno tation and they should not detract from the diagnosis of a virus-predominant disorder. Some patients may not respond to interferon treatment, but this lack of response does not negate the initial management strategy [27],…”

Section: Autoantigen-driven Immune Diseasesmentioning

confidence: 99%

Extrahepatic Immunologic Features of Chronic Viral Hepatitis

Czaja¹

1997

Dig Dis

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Patients with chronic viral hepatitis commonly have immunologic manifestations, including autoantibodies and concurrent immune diseases. These immunologic findings may resemble those of autoimmune hepatitis and they are not disease specific. High titer autoantibodies (titers ≧ 1:320) are uncommon in chronic viral hepatitis as are multiple concurrent autoantibodies. These findings reflect an autoimmune-predominant disorder in which the viral infection may be coincidental or facilitative. Concurrent immunologic disorders may be viral antigen-driven and associated with immune complex deposition (cryoglobulinemia, glomerulonephritis, cutaneous vasculitis, and polyarteritis) or autoantigen-driven (autoimmune thyroiditis and Sjögren’s syndrome) and associated with host- rather than virus-specific factors. Genetic predispositions influence immunologic expression. Seropositivity for antinuclear antibodies is associated with HLA A1-B8-DR3, and concurrent immunologic diseases are associated with the DR4 allele. Interferon therapy is appropriate for patients with viral antigen-driven processes that depend on immune complex deposition and for patients with mild background autoimmune expressions. Corticosteroid therapy should be considered for those unusual patients with predominant autoantigen-driven processes since interferon treatment may exacerbate immune-mediated diseases. Patients with chronic hepatitis B and C can have similar immune features, but patients with chronic hepatitis C more commonly have autoantigen-driven processes.

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“…Todros et al [24] from Turin reported on 33 LKM-positive patients, 24 of whom had anti-HCV antibodies in both the ELISA and RIBA. Only 3 of the 9 anti-HCV-negative patients appeared to have AIH, the others were suffering from toxic hepatitis or extrahepatic diseases.…”

Section: Lkm Autoantibodies and Hcv Infectionmentioning

confidence: 98%