Oral Presentation 9th Australasian Virology Society Meeting 2017

Immune Reconstitution after Allogeneic Haematopoietic Stem Cell Transplantation and its Relation to Human Cytomegalovirus Reactivation (#52)

Lauren Stern 1 , Selmir Avdic , Helen McGuire 2 , Caryn van Vreden 2 , Emily Blyth 3 , Angela Bayley 3 , Elissa Atkins 3 , Allison Abendroth 4 , David Gottlieb 3 , Barry Slobedman 4
  1. Infectious Diseases and Immunology, University of Sydney, Sydney, NSW, Australia, equal contribution
  2. Ramaciotti Facility for Human Systems Biology (RFHSB), University of Sydney and Centenary Institute, Sydney, NSW, Australia
  3. Dept Haematology, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
  4. Infectious Diseases and Immunology, University of Sydney, Sydney, NSW, Australia

Human cytomegalovirus (HCMV) is a ubiquitous and clinically important β-herpesvirus which establishes lifelong latency in myeloid progenitor cells. While HCMV infection is usually asymptomatic in healthy individuals, reactivation of HCMV from latency in contexts of compromised or suppressed immunity can result in potentially life-threatening end-organ disease. For allogeneic haematopoietic stem cell transplant (HSCT) recipients, opportunistic HCMV reactivation represents a leading post-transplant infectious complication. In the absence of prophylaxis, up to 80% of latently-infected HSCT recipients experience HCMV reactivation; but intriguingly, there are a proportion of latently-infected patients who appear to be protected from post-transplant HCMV reactivation. Given the importance of the host immune system in regulating the outcome of HCMV infection, we sought to explore whether certain profiles of post-transplant immune reconstitution might be associated with protection or predisposition to HCMV reactivation after HSCT. Mass cytometry (CyTOF) analysis of peripheral blood mononuclear cell (PBMC) samples collected from HSCT recipients (n=8) in the first 100 days post-transplant was used to track the reconstitution of multiple immune cell populations at time-points preceding, during and following clinical HCMV reactivation. Prior to the detection of HCMV reactivation, elevated proportions of intermediate and non-classical monocytes, activated and exhausted (PD-1+) T cells, and CD16+ NK cells, were observed in patients who subsequently developed HCMV reactivation (n=3), compared to those who did not experience reactivation (n=5). In addition, expanded percentages of CD8+ T cells, diminished proportions of B cells and an overrepresentation of non-classical monocytes were observed at the peak of HCMV reactivation, indicating a potential influence of viral reactivation on the pattern of cellular immune reconstitution in the early period post-HSCT. These data provide the foundation for ongoing studies with an expanded patient cohort into the immune parameters surrounding HCMV reactivation post-HSCT.