Humoral and cellular immunity to primary H1N1 infection in patients with hematologic malignancies following stem cell transplantation

Biol Blood Marrow Transplant. 2011 May;17(5):632-9. doi: 10.1016/j.bbmt.2010.08.002. Epub 2010 Aug 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies / analysis
  • Antibodies / immunology
  • CD40 Ligand / analysis
  • Case-Control Studies
  • Female
  • Hemagglutination Inhibition Tests
  • Hematologic Neoplasms / immunology*
  • Hematologic Neoplasms / pathology
  • Humans
  • Immunity, Cellular*
  • Immunity, Humoral*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control
  • Interferon-gamma / analysis
  • Interferon-gamma / biosynthesis
  • Lysosomal-Associated Membrane Protein 1 / analysis
  • Male
  • Middle Aged
  • Prospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cell Transplantation
  • Transplantation, Homologous

Substances

  • Antibodies
  • Lysosomal-Associated Membrane Protein 1
  • CD40 Ligand
  • Interferon-gamma