Karolinska Institutet, Department of Medicine at Huddinge University Hospital, Publisher, Karolinska Institutet, Institutionen för medicin, Huddinge Sjukhus, Publisher
Recipients of allogeneic hematopoietic stem cell transplantation(allo-HSCT) experience a prolonged period of immune deficiency, resultingin significant morbidity and mortality from the infections. Viruses suchas cytomegalovirus (CMV) and influenza virus are frequent causes ofinfectious complications following allo-HSCT.CMV is one of the most frequent pathogens causing life-threateningcomplications after HSCT. Factors like patient age, donor and recipientserostatus, type of conditioning, grade of graft versus host disease(GVHD), CMV viremia and number of CMV reactivations are all factorsinfluencing virus reactivation and contributing to the development of thedisease. Although CMV infection can be controlled by pre-emptivetreatment based on sensitive diagnostic tests, there is a risk ofunnecessary over-treatment, resulting in development of antiviralresistance and late onset of CMV disease. In our two CMV studies we aimedin paper I to use the immunological monitoring of CMV-specific responsesto correlate transplantation factors to the recovery of cellular immunityin HSCT recipients, intending to understand how those factors influencethe CMV-specific T cell reconstitution. The aim of paper II was to usethe CMV-specific immunological monitoring to target antiviral therapy topatients at the highest risk of developing CMV disease. By correlatingthe intracellular interferon-gamma (IFN-γ) production by CMV-specific Tlymphocytes with transplant factors (paper I) we observed that (a)CMV-specific T cell response is associated with a lower rate of CMVreplication; (b) reduced intensity conditioning results in improved earlyT cell reconstitution; and (c) the recovery of CMV-specific immunitymight be delayed in patients with CMV disease. Using the same method ofmonitoring CMV-specific immunity in the second study (paper II) we foundthat 25% of patients with late CMV DNAemia, who had CMV-specific immunityand lacked other risk factors of CMV disease, could be spared pre-emptivetherapy without developing CMV disease or need of anti-viral therapy.Annual vaccination is the main way to prevent influenza and itscomplications, but it is less effective in immunocompromised patientscompared to healthy individuals. Since most previous studies ofvaccination efficacy investigated the humoral immune response, we aimedto develop an Elispot technique for measuring the influenza-specificcellular response as a marker of vaccine responsiveness (paper III). Wemeasured the IFN- γ production by T cells pulsed with influenza peptidesin healthy volunteers and HSCT recipients. Influenza vaccination elicitedstrong cell-mediated immune response in the group of healthy volunteersand we concluded that Elispot is a sensitive and specific assay formeasuring cell-mediated immunity to vaccination. To further explore theresponses to vaccination, we applied two Elispot methods to characterizeboth the cell-mediated and humoral responses to influenza vaccination(study IV). The cell-mediated responses were strong both in the healthyvolunteers and in the transplanted patients. However, we found a bigdifference in the number of influenza-specific antibody secreting cellsbetween healthy controls and HSCT patients, both before and aftervaccination, supporting the previously shown weak ability of transplantedpatients to respond to vaccination with a protective antibody response.In conclusion, routine immunologic monitoring will be helpful in guidingvirological monitoring and therapeutic decisions in HSCT recipients. Theinactivated split influenza vaccination elicits cell-mediated and humoralimmune responses in HSCT recipients. In spite of that, the effectivenessof the vaccination in immunocompromised patients is low, which highlightsthe need of more immunogenic vaccine formulations for this population.
