Localization of hepatitis C virus antigens in liver and skin tissues of chronic hepatitis C virus–infected patients with mixed cryoglobulinemia

Authors

  • Domenico Sansonno MD,

    Corresponding author
    1. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, Bari, Italy
    • Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Policlinico, P.zza G. Cesare 11, 70124 Bari, Italy
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  • Vito Cornacchiulo,

    1. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, Bari, Italy
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  • Anna Rina Iacobelli,

    1. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, Bari, Italy
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  • Rita Di Stefano,

    1. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, Bari, Italy
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  • Mario Lospalluti,

    1. Institute of Dermatology, University of Bari Medical School, Bari, Italy
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  • Franco Dammacco

    1. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, Bari, Italy
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Abstract

Skin and/or liver biopsy specimens were obtained from the following patients: 15 anti–hepatitis C virus (HCV), HCV RNA–positive patients and 3 anti-HCV, HCV RNA–negative patients with type II mixed cryoglobulinemia (MC); 7 anti-HCV, HCV RNA–positive patients with chronic active liver disease (CALD); 5 anti-HCV, HCV RNA–negative patients with noncryoglobulinemic vasculitis; and 7 anti-HCV, HCV RNA–negative patients with 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 electroelution (AEE) of tissue sections was performed to enhance the sensitivity of the immunohistochemical method. In anti-HCV–positive MC patients, specific HCV-related Ags were detected in the small vessels of the skin and in the cytoplasm of hepatocytes. Prior AEE of biopsy sections allowed detection of HCV Age 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 intraluminal material associated with dermal inflammatory infiltrates and intravascular deposition of eosinophilic hyaline material; and (2) reactivity confined to the vessel wall in the context of an apparently normal tissue. Immunoglobulin (Ig) G and IgM deposition in the skin showed 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 clinical signs of active vasculities. Five of 7 (71.4%) liver biopsy specimens, but none of 7 skin biopsy specimens, from anti-HCV, HCV RNA–positive patients without circulating 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 deposits consist of HCV-containing immune complexes. In addition, the occurrence of HCV reactivity in apparently normal blood vessels suggests that deposition of viral Ags precedes and possibly initiates tissue damage. Whether in the remaining patients HCV Ags cannot be detected because of the insufficient sensitivity of the method or the involvement of Ags other than those assayed, remains to be determined. (HEPATOLOGY 1995;21:305–312.)

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