LOCALIZATION OF HEPATITIS-C VIRUS-ANTIGENS IN LIVER AND SKIN TISSUES OF CHRONIC HEPATITIS-C VIRUS - INFECTED PATIENTS WITH MIXED CRYOGLOBULINEMIA

Skin and/or liver biopsy specimens were obtained from the following pa tients: 15 anti-hepatitis C virus (HCV), HCV RNA-positive patients and 3 anti-HCV, HCV RNA-negative patients with type II mixed cryoglobulin emia (MC); 7 anti-HCV, HCV RNA-positive patients with chronic active l iver disease (CALD); 5 anti-HCV, HCV RNA-negative patients with noncry oglobulinemic vasculitis; and 7 anti-HCV, HCV RNA-negative patients wi th lichen ruber planus. A pool of murine monoclonal antibodies (MAbs) developed against c22-3, c33c, and c100-3 proteins was used to detect HCV-related antigens (Ags) by indirect immunohistochemistry. Acid elec tro-elution (AEE) of tissue sections was performed to enhance the sens itivity of the immunohistochemical method. In anti-HCV-positive MC pat ients, specific HCV-related Ags were detected in the small vessels of the skin and in the cytoplasm of hepatocytes. Prior AEE of biopsy sect ions allowed detection of HCV Ags in 6 of 15 (40%) skin biopsy and in 9 of 14 (64.3%) liver biopsy specimens. HCV immunoreactive deposits in the skin displayed two immunohistochemical patterns: (1) coarse intra luminal material associated with dermal inflammatory infiltrates and i ntravascular deposition of eosinophilic hyaline material; and (2) reac tivity confined to the vessel wall in the context of an apparently nor mal tissue. Immunoglobulin (Ig) G and IgM deposition in the skin showe d immunohistochemical features comparable with those found for HCV Ag deposits. In addition, tissue complement reactivity was detected in 6 (40%) of them and was strictly associated with histological and clinic al signs of active vasculitis. Five of 7 (71.4%) liver biopsy specimen s, but none of 7 skin biopsy specimens, from anti-HCV, HCV RNA-positiv e patients without circuling cryoglobulins displayed immune reactivity after AEE procedure. Consistently negative results were obtained with skin and liver sections from all anti-HCV, HCV RNA-negative patients. These findings indicate that, under the experimental conditions used, in 40% of anti-HCV, HCV RNA-positive patients with MC, skin tissue de posits consist of HCV-containing immune complexes. In addition, the oc currence of HCV reactivity in apparently normal blood vessels suggests that deposition of viral Ags precedes and possibly initiates tissue d amage. Whether in the remaining patients HCV Ags cannot be detected be cause of the insufficient sensitivity of the method or the involvement of Ags other than those assayed, remains to be determined.