Up-regulation of the monocyte chemotactic protein-3 in sera from bone marrow transplanted children with torquetenovirus infection

Background: Torquetenovirus (TTV) represents a commensal human virus producing life-long viremia in approximately 80% of healthy individuals of all ages. A potential pathogenic role for TTV has been suggested in immunocompromised patients with hepatitis of unknown etiology sustained by strong proinflammatory cytokines.

Objectives: The aim of this study was to investigate the sera immunological profile linked to TTV infection in bone marrow transplant (BMT) children with liver injury.

Study design: TTV infection was assessed in sera from 27 BMT patients with altered hepatic parameters and histological features, by the use of quantitative real-time PCR, along with TTV genogroups and coinfection with HEV. The qualitative and quantitative nature of soluble inflammatory factors was evaluated studying a large set of cytokines using the Bioplex platform. As controls, sera from 22 healthy children negative for serological and molecular hepatitis markers including TTV and HEV, and for autoimmune diseases, were selected.

Results and conclusions: TTV was detected in 81.4% of BMT patients with a viral load ranging from 10(5) to 10(9) copies/mL. All samples were HEV-RNA negative. A pattern of cytokines, IFN-γ, TNF-α, FGF-basic (p<0.01) and MCP-3 (p<0.001) was found significantly highly expressed in TTV-positive patients compared to TTV-negative and controls. Of note, MCP-3 chemokine showed the highest sera concentration independently of the amount of TTV load and the status of immune system deregulation (p<0.001). In this pilot study for the first time, a positive association was found between TTV and increased level of MCP-3 suggesting a indirect role of TTV in liver injury.