A group from the University of Nantes (France) has reported new findings which may help explain the mystery behind the increased rates of HHV-6 reactivation and encephalitis observed among umbilical cord blood transplant (CBT) patients compared with those undergoing traditional transplantation. This disproportional reactivation of HHV-6 compared to CMV, EBV and other pathogens in CBT patients has garnered attention from the transplant community due to the high rate of HHV-6 encephalitis (8-10%) resulting in a high level of death and disability.
The study, led by Drs. Chevallier and Imbert-Marcille, suggests several reasons why HHV-6 reactivation is elevated in CBT patients. The group studied the differential expression of CD46—the chief HHV-6 cell receptor—among various subsets of blood and graft sources used in transplantation. The group determined that CD46 expression itself is likely not the only factor contributing to the increased rate of HHV-6 reactivation among CBT patients. They found no difference in CD46 expression between thawed CB grafts (the true condition of clinical administration) and other traditional sources of stem cells.
This unexpected finding is an important clarification and will encourage others to investigate other possible reasons for this preferential HHV-6 reactivation. Chevalier et al propose several alternative factors that could be at play, including the expression of another HHV-6 cell surface receptor (for HHV-6B in particular), higher percentage of available CD4+ T cells, and the differential level of plasmacytoid dendritic cells (pDCs) observed in CB graft. The group urges continued investigation of these alternative possibilities moving forward.