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

ObjectivesType 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.MethodsPeripheral 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.ResultsNegative 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.ConclusionOur 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.