Autoantibodies and Autoantigens in Autoimmune Hepatitis

Christian P. Strassburg, MD, Michael P. Manns, MD

Disclosures

Semin Liver Dis. 2002;22(4) 

In This Article

Hepatitis C-Associated Microsomal Autoantibodies

Hepatitis C is associated with an array of extrahepatic manifestations, including mixed cryoglobulinemia, membranoproliferative glomerulonephritis, polyarthritis, porphyria cutanea tarda, Sjögren's syndrome, and autoimmune thyroid disease.[95,96,97,98] Not surprisingly, numerous autoantibodies are associated with chronic hepatitis C. Similar to AIH ANA, SMA, LKM, and antithyroid antibodies are found with a high prevalence. An HCV-specific autoantibody, designated anti-GOR, that is present in at least 80% of sera from patients with hepatitis C was described.[99] However, anti-GOR seems to be anti-hepatitis C core antibodies cross-reacting with a nuclear self-antigen rather than being a proper autoantibody. This assumption is based on the fact that anti-GOR disappears once HCV replication has stopped.

The examination of LKM autoantibodies in HCV patients revealed that, although anti-CYP 2D6 titers are similar to titers in AIH type 2, differences exist regarding the epitopes recognized by LKM autoantibodies.[63,100,101,102] In patients with AIH type 2, the epitope of aa 257-269 is recognized with a significantly higher prevalence than in chronic hepatitis C.[101] In addition, the immune reaction seems to be more heterogenous than in AIH, as indicated by recognized protein targets of 59 kD and 70 kD.[92]

LKM autoantibodies in chronic hepatitis C seem to indicate an increased risk of exacerbation of the disease.[62,103,104] Dalekos et al[62] studied antibody titers and performed epitope mapping of LKM-1-positive sera from patients with chronic hepatitis C. Interestingly, a patient with a high LKM-1 titer and autoantibodies directed against an epitope of aa 257-269, which is preferentially recognized by patients with AIH-2, showed exacerbation of the disease under interferon treatment. In contrast to other patients with HCV infection, this patient further recognized a rarely detected epitope on the C-terminal third of the protein. These results suggest that epitope mapping might be helpful to detect patients at risk of exacerbation of disease.[62]

Recently, another autoantibody was detected in patients infected with HCV and the hepatitis G (HGV)/ GB-virus subtype C. About 2% of HCV-positive sera in general and 7.5% of LKM-1-positive HCV sera recognize CYP 2A6. This autoantibody appears to occur more frequently in HCV-infected patients with LKM-1 autoantibodies. Interestingly, anti-CYP 2A6 autoantibodies are not detected in patients with AIH type 2 who exhibit high titers of LKM-1 autoantibodies. The clinical relevance of this finding remains to be determined.[74] Anti-CYP 2A6 autoantibodies have also been detected in patients with APS-1.[24]

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