Humoral and cellular immunity to primary H1N1 infection in patients with hematologic malignancies following stem cell transplantation.
Limited data are available on immunologic responses to primary H1N1 infection in patients with hematologic malignancies. We present a prospective, case-surveillance study of such patients with real-time polymerase chain reaction (RT-PCR) confirmed H1N1-influenza who presented to our institution between September 2009 and January 2010. Ninety-two patients presented with influenza-like symptoms, and 13 had H1N1 infection confirmed by RT-PCR, including 4 allogeneic stem cell transplant recipients (1 with acute myelogenous leukemia, 1 with chronic lymphoblastic leukemia [CLL], 1 with non-Hodgkin lymphoma, and 1 with chronic myelogenous leukemia), 5 patients with multiple myeloma following autologous stem cell transplantation, 1 patient with multiple myeloma perimobilization, 2 patients with NHL post chemotherapy, and 1 patient with CLL. All 13 patients required hospitalization. Six (43%) were admitted to the intensive care unit (ICU), of whom 4 (67%) died. We evaluated B cell and T cell responses to H1N1 infection prospectively in these patients compared with those in 4 otherwise healthy controls. Within 12 weeks of diagnosis, only 6 of 11 patients developed seropositive antibody titers as measured by hemagglutination-inhibition or microneutralization assays, compared with 4 of 4 controls. H1N1-specific T cells were detected in only 2 of 8 evaluable patients compared with 4 of 4 controls. H1N1-specific T cells were functional, capable of producing interferon γ, tumor necrosis factor α, and CD107a mobilization. Furthermore, CD154 was up-regulated on CD4(+) T cells in 3 of 4 controls and 2 of 2 patients who had both B cell and T cell responses to H1N1. Post-H1N1 infection, 5 of 8 patients developed seasonal influenza-specific T cells, suggesting cross-reactivity induced by H1N1 infection. These data offer novel insights into humoral and cell-mediated immunologic responses to primary H1N1 infection.
Garland
Paula
P
Department of Hematology, Imperial College London, London, UK.
de Lavallade
Hugues
H
Sekine
Takuya
T
Hoschler
Katja
K
Sriskandan
Shiranee
S
Patel
Parind
P
Brett
Stephen
S
Stringaris
Kate
K
Loucaides
Eva
E
Howe
Katherine
K
Marin
David
D
Kanfer
Ed
E
Cooper
Nichola
N
Macdonald
Donald
D
Rahemtulla
Amin
A
Atkins
Mark
M
Danga
Akila
A
Milojkovic
Dragana
D
Gabriel
Ian
I
Khoder
Ahmad
A
Alsuliman
Abdullah
A
Apperley
Jane
J
Rezvani
Katayoun
K
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D023201:CD40 Ligand / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
D000906:Antibodies; D052118:Lysosomal-Associated Membrane Protein 1; D023201:CD40 Ligand; D007371:Interferon-gamma