Studies of specific immunity against viral infections in patients after stem cell transplantation
Author: Avetisyan, Gayane
Date: 2007-11-02
Location: Föreläsningssalen, M63, Karolinska Universitetssjukhuset, Huddinge
Time: 09.00
Department: Institutionen för medicin, Huddinge Sjukhus / Department of Medicine at Huddinge University Hospital
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Abstract
Recipients of allogeneic hematopoietic stem cell transplantation
(allo-HSCT) experience a prolonged period of immune deficiency, resulting
in significant morbidity and mortality from the infections. Viruses such
as cytomegalovirus (CMV) and influenza virus are frequent causes of
infectious complications following allo-HSCT.
CMV is one of the most frequent pathogens causing life-threatening
complications after HSCT. Factors like patient age, donor and recipient
serostatus, type of conditioning, grade of graft versus host disease
(GVHD), CMV viremia and number of CMV reactivations are all factors
influencing virus reactivation and contributing to the development of the
disease. Although CMV infection can be controlled by pre-emptive
treatment based on sensitive diagnostic tests, there is a risk of
unnecessary over-treatment, resulting in development of antiviral
resistance and late onset of CMV disease. In our two CMV studies we aimed
in paper I to use the immunological monitoring of CMV-specific responses
to correlate transplantation factors to the recovery of cellular immunity
in HSCT recipients, intending to understand how those factors influence
the CMV-specific T cell reconstitution. The aim of paper II was to use
the CMV-specific immunological monitoring to target antiviral therapy to
patients at the highest risk of developing CMV disease. By correlating
the intracellular interferon-gamma (IFN-γ) production by CMV-specific T
lymphocytes with transplant factors (paper I) we observed that (a)
CMV-specific T cell response is associated with a lower rate of CMV
replication; (b) reduced intensity conditioning results in improved early
T cell reconstitution; and (c) the recovery of CMV-specific immunity
might be delayed in patients with CMV disease. Using the same method of
monitoring CMV-specific immunity in the second study (paper II) we found
that 25% of patients with late CMV DNAemia, who had CMV-specific immunity
and lacked other risk factors of CMV disease, could be spared pre-emptive
therapy without developing CMV disease or need of anti-viral therapy.
Annual vaccination is the main way to prevent influenza and its
complications, but it is less effective in immunocompromised patients
compared to healthy individuals. Since most previous studies of
vaccination efficacy investigated the humoral immune response, we aimed
to develop an Elispot technique for measuring the influenza-specific
cellular response as a marker of vaccine responsiveness (paper III). We
measured the IFN- γ production by T cells pulsed with influenza peptides
in healthy volunteers and HSCT recipients. Influenza vaccination elicited
strong cell-mediated immune response in the group of healthy volunteers
and we concluded that Elispot is a sensitive and specific assay for
measuring cell-mediated immunity to vaccination. To further explore the
responses to vaccination, we applied two Elispot methods to characterize
both the cell-mediated and humoral responses to influenza vaccination
(study IV). The cell-mediated responses were strong both in the healthy
volunteers and in the transplanted patients. However, we found a big
difference in the number of influenza-specific antibody secreting cells
between healthy controls and HSCT patients, both before and after
vaccination, supporting the previously shown weak ability of transplanted
patients to respond to vaccination with a protective antibody response.
In conclusion, routine immunologic monitoring will be helpful in guiding
virological monitoring and therapeutic decisions in HSCT recipients. The
inactivated split influenza vaccination elicits cell-mediated and humoral
immune responses in HSCT recipients. In spite of that, the effectiveness
of the vaccination in immunocompromised patients is low, which highlights
the need of more immunogenic vaccine formulations for this population.
List of papers:
I. Avetisyan G, Larsson K, Aschan J, Nilsson C, Hassan M, Ljungman P (2006). "Impact on the cytomegalovirus (CMV) viral load by CMV-specific T-cell immunity in recipients of allogeneic stem cell transplantation." Bone Marrow Transplant 38(10): 687-92. Epub 2006 Sep 25
Pubmed
II. Avetisyan G, Aschan J, Hägglund H, Ringdén O, Ljungman P (2007). "Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT." Bone Marrow Transplant Aug 27: Epub ahead of print
Pubmed
III. Avetisyan G, Ragnavölgyi E, Toth GT, Hassan M, Ljungman P (2005). "Cell-mediated immune responses to influenza vaccination in healthy volunteers and allogeneic stem cell transplant recipients." Bone Marrow Transplant 36(5): 411-5
Pubmed
IV. Avetisyan G, Aschan J, Hassan M, Ljungman P (2007). "Studies of immune responses to seasonal influenza vaccination in healthy volunteers and in patients after stem cell transplantation." (Submitted)
I. Avetisyan G, Larsson K, Aschan J, Nilsson C, Hassan M, Ljungman P (2006). "Impact on the cytomegalovirus (CMV) viral load by CMV-specific T-cell immunity in recipients of allogeneic stem cell transplantation." Bone Marrow Transplant 38(10): 687-92. Epub 2006 Sep 25
Pubmed
II. Avetisyan G, Aschan J, Hägglund H, Ringdén O, Ljungman P (2007). "Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT." Bone Marrow Transplant Aug 27: Epub ahead of print
Pubmed
III. Avetisyan G, Ragnavölgyi E, Toth GT, Hassan M, Ljungman P (2005). "Cell-mediated immune responses to influenza vaccination in healthy volunteers and allogeneic stem cell transplant recipients." Bone Marrow Transplant 36(5): 411-5
Pubmed
IV. Avetisyan G, Aschan J, Hassan M, Ljungman P (2007). "Studies of immune responses to seasonal influenza vaccination in healthy volunteers and in patients after stem cell transplantation." (Submitted)
Issue date: 2007-10-12
Rights:
Publication year: 2007
ISBN: 978-91-7357-339-9
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