Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation and Association With Occurrence and Outcome of Invasive Aspergillosis.
BACKGROUND
Invasive aspergillosis (IA) remains a leading cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To date, no reliable immunological biomarkers for management and outcome of IA exist. Here, we investigated reconstitution of antifungal immunity in patients during the first 12 months after HSCT and correlated it with IA.


METHODS
Fifty-one patients were included, 9 with probable/proven IA. We determined quantitative and qualitative reconstitution of polymorphonuclear (PMN), CD4, CD8, and natural killer (NK) cells against Aspergillus fumigatus over 5 time points and compared the values to healthy donors.


RESULTS
Absolute CD4 and CD8 cell counts, antigen-specific T-cell responses, and killing capacity of PMN against A. fumigatus were significantly decreased in all patients over 12 months. In patients with probable/proven IA, reactive oxygen species (ROS) production tended to be lower compared to patients without IA, and absolute NK-cell counts remained below 200 cells/µL. Patients with well-controlled IA showed significantly higher ROS production and NK-cell counts compared to patients with poor outcome.


CONCLUSIONS
This study highlights the importance of functional PMN, T-cell, and NK-cell immunity for the outcome of IA. Larger multicenter studies should address the potential use of NK-cell counts for the management of antifungal therapy.
Infection Biology Laboratory, Department of Biomedicine.
Claudia
C
Stuehler
Division of Infectious Diseases and Hospital Epidemiology, Department of Clinical Research.
Esther
E
Kuenzli
Department of Rheumatology.
Veronika K
VK
Jaeger
Division of Infectious Diseases and Hospital Epidemiology, Department of Clinical Research.
Veronika
V
Baettig
Infection Biology Laboratory, Department of Biomedicine.
Fabrizia
F
Ferracin
Infection Biology Laboratory, Department of Biomedicine.
Zarko
Z
Rajacic
Infection Biology Laboratory, Department of Biomedicine.
Deborah
D
Kaiser
Infection Biology Laboratory, Department of Biomedicine.
Claudia
C
Bernardini
Infection Biology Laboratory, Department of Biomedicine.
Pascal
P
Forrer
Division of Infectious Diseases and Hospital Epidemiology, Department of Clinical Research.
Maja
M
Weisser
Division of Infectious Diseases and Hospital Epidemiology, Department of Clinical Research.
Luigia
L
Elzi
Division of Infectious Diseases and Hospital Epidemiology, Department of Clinical Research.
Manuel
M
Battegay
Division of Hematology, University Hospital of Basel, Switzerland.
Joerg
J
Halter
Division of Hematology, University Hospital of Basel, Switzerland.
Jakob
J
Passweg
Infection Biology Laboratory, Department of Biomedicine Division of Infectious Diseases and Hospital Epidemiology, Department of Clinical Research.
Nina
N
Khanna
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D001230:Aspergillus / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D049109:Cell Proliferation; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D016867:Immunocompromised Host; D055744:Invasive Pulmonary Aspergillosis / Q000276:immunology*; D007694:Killer Cells, Natural; D017382:Reactive Oxygen Species
D000305:Adrenal Cortex Hormones; D017382:Reactive Oxygen Species
HSCT; NK-cell count as immunological marker; antifungal innate and adaptive immunity; immune reconstitution