Abstract
Objectives It is established that autologous haematopoietic stem cell transplant (AHSCT) is a high-efficacy form of therapy for MS patients who have active disease despite pharmacotherapy; inducing protracted disease remission. Despite the import of EBV in MS pathogenesis no study has reviewed the effect of AHSCT on EBV viraemia, anti-EBV T and B cell immunity, nor latent viral load. Here, we study immune reconstitution which follows AHSCT to parse the role of EBV infection, anti-EBV immunity and its impact on MS.
Methods Bio-banked peripheral blood mononuclear cells (PBMCs) and platelet depleted plasma (PDP) were collected from MS patients enrolled in a phase 2 clinical trial (ACTRN12613000339752) pre-AHSCT, and at months 3, 6, 12, 24 and 36 post-AHSCT, n=22. Repertoire sequencing of TCRb chains were amplified from FAC-sorted CD4/CD8 naïve and memory cells. Longitudinal EBV-avid TCR responses were assessed through HLA-restricted repositories (VDJdb.com). EBNA IgG titres were analysed using the Abbott EBNA IgG kit. EBV viraemia and EBV genome load per cell was calculated using qPCR.
Results EBV DNAemia was rare beyond 3 months post-AHSCT, occurring in 3/22 individuals. DNAemia correlated with detectable EBV-specific T cell responses, clonal expansions of CD8+45RO+ T cells targeting both lytic and latent EBV epitopes. EBNA1 titres were preserved in 19 patients, and fell in 3 patients, all of whom relapsed post-AHSCT. EBV genome load within memory B cells increased concurrent with relapse in a single patient, 13 months post-AHSCT.
Conclusions Perturbations in EBV viral load and anti-EBV immunity appear to associate with relapse post-AHSCT.
