Studies of Specific Immunity Against Viral Infections After Stem Cell Transplantation
Year: 2007
Type: dissertation
Abstract: Recipients of allogeneic hematopoietic stem cell transplantation\n(allo-HSCT) experience a prolonged period of immune deficiency, resulting\nin significant morbidity and mortality from the infections. Viruses such\nas cytomegalovirus (CMV) and influenza virus are frequent causes of\ninfectious complications following allo-HSCT.\n\nCMV is one of the most frequent pathogens causing life-threatening\ncomplications after HSCT. Factors like patient age, donor and recipient\nserostatus, type of conditioning, grade of graft versus host disease\n(GVHD), CMV viremia and number of CMV reactivations are all factors\ninfluencing virus reactivation and contributing to the development of the\ndisease. Although CMV infection can be controlled by pre-emptive\ntreatment based on sensitive diagnostic tests, there is a risk of\nunnecessary over-treatment, resulting in development of antiviral\nresistance and late onset of CMV disease. In our two CMV studies we aimed\nin paper I to use the immunological monitoring of CMV-specific responses\nto correlate transplantation factors to the recovery of cellular immunity\nin HSCT recipients, intending to understand how those factors influence\nthe CMV-specific T cell reconstitution. The aim of paper II was to use\nthe CMV-specific immunological monitoring to target antiviral therapy to\npatients at the highest risk of developing CMV disease. By correlating\nthe intracellular interferon-gamma (IFN-γ) production by CMV-specific T\nlymphocytes with transplant factors (paper I) we observed that (a)\nCMV-specific T cell response is associated with a lower rate of CMV\nreplication; (b) reduced intensity conditioning results in improved early\nT cell reconstitution; and (c) the recovery of CMV-specific immunity\nmight be delayed in patients with CMV disease. Using the same method of\nmonitoring CMV-specific immunity in the second study (paper II) we found\nthat 25% of patients with late CMV DNAemia, who had CMV-specific immunity\nand lacked other risk factors of CMV disease, could be spared pre-emptive\ntherapy without developing CMV disease or need of anti-viral therapy.\n\nAnnual vaccination is the main way to prevent influenza and its\ncomplications, but it is less effective in immunocompromised patients\ncompared to healthy individuals. Since most previous studies of\nvaccination efficacy investigated the humoral immune response, we aimed\nto develop an Elispot technique for measuring the influenza-specific\ncellular response as a marker of vaccine responsiveness (paper III). We\nmeasured the IFN- γ production by T cells pulsed with influenza peptides\nin healthy volunteers and HSCT recipients. Influenza vaccination elicited\nstrong cell-mediated immune response in the group of healthy volunteers\nand we concluded that Elispot is a sensitive and specific assay for\nmeasuring cell-mediated immunity to vaccination. To further explore the\nresponses to vaccination, we applied two Elispot methods to characterize\nboth the cell-mediated and humoral responses to influenza vaccination\n(study IV). The cell-mediated responses were strong both in the healthy\nvolunteers and in the transplanted patients. However, we found a big\ndifference in the number of influenza-specific antibody secreting cells\nbetween healthy controls and HSCT patients, both before and after\nvaccination, supporting the previously shown weak ability of transplanted\npatients to respond to vaccination with a protective antibody response.\n\nIn conclusion, routine immunologic monitoring will be helpful in guiding\nvirological monitoring and therapeutic decisions in HSCT recipients. The\ninactivated split influenza vaccination elicits cell-mediated and humoral\nimmune responses in HSCT recipients. In spite of that, the effectiveness\nof the vaccination in immunocompromised patients is low, which highlights\nthe need of more immunogenic vaccine formulations for this population.
Source: Figshare
Author: Gayane Avetisyan
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2100578961