Interferon-γ and interleukin-2 in patients with acute graft-versus-host disease and infectious complications after allogeneic hematopoietic stem cell transplantation
Abstract
Introduction
The allogeneic Hematopoietic Stem Cells Transplantation (alloHSCT) is associated with the risk of Graft versus Host Disease (GvHD) and infections. The pathogenesis of acute GvHD is related to T-lymphocytes, which identify alloantigens on host's Antigen Presenting Cells, induce production of IFN-γ and IL-2, recruit the immunological effectory cells and destroy tissues and organs.
Aim
The aim of the study was to analyse the relationship between IL-2 and IFN-γ serum concentrations and acute GvHD and infections.
Material and methods
The study involved 62 patients, 30 (48%) male and 32 (52%) female, aged at median 49.5 (19–68) years, after alloHSCT from sibling (n=12) or from unrelated donor (n=50) performed for acute myeloid leukemia (AML) with myeloablative conditioning (n=26, 42%) and with non-myeloablative conditioning (n=36, 58%) in Katowice in years 2012–2014. All patients received standard immunosuppressive therapy with cyclosporin-A and methotrexate plus pre-transplant anti-thymocyte globulin in unrelated setting. Blood samples were collected pre-transplant before start and after (on day -1) the conditioning therapy and on days +2 +4, +6, +10, +20, +30 after alloHSCT. The IL-2 and IFN-γ serum concentrations were determined with use of ELISA assay. Before statistical analysis patients were divided into 4 groups according to the presence of acute GvHD and clinical manifestation of bacterial, viral or fungal infection.
Results
Group I – patients with neither acute GvHD nor infectious complications, n=15 (24%), group II – patients with infectious complications without acute GvHD, n=17 (27%), group III – patients with acute GvHD without infectious complications, n=9 (15%), and group IV – patients with both acute GvHD and infectious complications, n=21 (34%). IFN-γ levels were higher in group II than in other groups on days +20 (p=0.014) and +30 (p=0.008). The POST-HOC tests revealed lower levels of IFN-γ on day +30 in group I (p=0.039) and in group IV (p=0.017) as compared to group II. The concentration of IL-2 was undetectable in almost all patients at all studied time points.
Conclusion
Serum concentration of IFN-γ following alloHSCT gradually increases. High serum concentration of IFN-γ is related to infectious complications rather than to acute GvHD. Undetectable serum concentration of IL-2 in majority of patients prevents from drawing conclusions.
Keywords: Interleukin-2Interferon-γAcute Myeloid LeukemiaAllogeneic stem cell transplantationAcute graft-versus-host disease