A Simple Proteomics-Based Approach to Identification of Immunodominant Antigens from a Complex Pathogen: Application to the CD4 T Cell Response against Human Herpesvirus 6B
BACKGROUND AND METHODS To study clinical symptoms, timing and consequences of human herpesvirus-6 (HHV-6) reactivation after pediatric allogeneic stem cell transplantation (SCT), HHV-6 was investigated by plasma polymerase chain reaction in a cohort of 106 pediatric SCT recipients. RESULTS HHV-6 viremia was detected post-SCT in 48% of the patients with a median time of onset at 20 days after SCT. In week 3 and 4 post-SCT, HHV-6 is the most common infectious agent detected. In up to 30% of the patients with fever of unknown origin, HHV-6 was the only detected infectious agent to explain fever. Patients transplanted with an unrelated donor or receiving serotherapy were at increased risk of HHV-6 reactivation. The onset of HHV-6 reactivation coincided with the appearance of lymphocytes and monocytes in peripheral blood. Treatment with alemtuzumab (MabCampath) delayed both lymphocyte and monocyte engraftment and, concomitantly, onset of HHV-6 reactivation was delayed in those cases. HHV-6 reactivation was not associated with an increased incidence of acute graft-versus-host disease (GvHD). However, progression to grade II-IV GvHD was in 9 of 10 patients associated with HHV-6 reactivation before GvHD (P = 0.006) and HHV-6 was the only infection with such an association. CONCLUSIONS HHV-6 frequently reactivates after pediatric SCT around the time of mononuclear cell engraftment and is associated with an increased severity of GvHD. HHV-6 may explain fever of unknown origin in 30% of the patients early after SCT. Assessment of HHV-6 reactivation in patients early after SCT can be instrumental for clinical decision making.