Primary and Secondary Infections by Human Parvovirus B19 following Bone Marrow Transplantation: Characterization by PCR and B-Cell Molecular Immunology

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Abstract
Due to the preparative regimen necessary, bone marrow transplantation (BMT) consistently results in severe immunodeficiency, often associated with anaemia, leukopenia and thrombocytopenia. Parvovirus B19 replicates in red blood cell precursors in the bone marrow and causes erythema infectiosum ('fifth disease'), anaemia, arthritis and foetal death. We assessed the significance of B19 infections as a cause of post-BMT complications. Over 900 serial serum samples from 201 allogeneic bone marrow recipients were studied by polymerase chain reaction (PCR) and by modern serodiagnostic methods. During the first 6 months after transplantation all BMT recipients remained B19 PCR-negative. Antibody screening for B19 infections was performed up to 36 months post-transplantation. Three cases of acute B19 infection were diagnosed during the second year post-BMT. To characterize the adoptively transferred immune system we measured subclasses and avidity of anti-VP1 IgG and epitope-type specificity (ETS) of anti-VP2 IgG, which allowed functional differentiation of primary and secondary B-cell responses long after BMT. The profile of the immune response was that of a primary infection in 1 and of reinfection in 2 of the 3 acute cases. Both types were clinically mild. Infection by human parvovirus B19 is not a frequent cause of post-BMT cytopenias. The findings with the new B19 antibody markers support the concept that the donated marrow determines the type of antiviral B-cell responses.