Hepatitis C virus (HCV) infection of peripheral blood mononuclear cells in patients with type II cryoglobulinemia.

OBJECTIVES: Type II cryoglobulinemia is a common extrahepatic manifestation of chronic hepatitis C virus (HCV) infection. The mechanisms behind its development are unclear, but could be related to direct infection of the immune cells.

METHODS: Peripheral blood mononuclear cells from 18 patients with type II cryoglobulinemia were separated into CD3+ (T cells), CD19+ (B cells) and CD14+ (monocytes) and analyzed for the presence of negative strand HCV RNA, which is a viral replicative intermediate, and for the presence of HCV non-structural protein 3 (NS3). Control group consisted of 182 consecutive chronic hepatitis C patients prior to initiation of antiviral therapy.

RESULTS: Negative strand HCV RNA was detected in PBMC from six (33.3%), patients and in 15 (8.2%) controls (p < 0.01). Negative strand was most frequently detected in B cells (3 patients), followed by T cells (2 patients), and monocytes (2 patients). One patient was positive both in CD3+ and CD14+ cells. NS3 protein was detected in six (33.3%) patients; five were positive in T cells, three in B cells, and another three were positive in monocytes. Two patients were positive in all analyzed cell subpopulation and one patient was positive in CD14+ and CD19+ cells, but not in CD3+ cells. Altogether, 11 patients (61.1%) were positive either for the negative strand HCV RNA or NS3 protein in at least one of the analyzed cell compartments.

CONCLUSION: Our findings of common presence of viral replication in cells of the immune system suggest that direct HCV infection could play a role in the etiology of cryoglobulinemia.