Chronic graft versus host disease is associated with an immune response to autologous human leukocyte antigen-derived peptides

Helen J. Smith, Rajesh Hanvesakul, Matthew D. Morgan, Andrew Bentall, David Briggs, Fiona Clark, Guy Pratt, Paul Moss, Mark Larché, Simon Ball

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background. Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation (BMT) the immunopathogenesis of which is not well understood. Humoral and cellular immunity are both implicated, patients express a range of autoantibodies, but the targets of cellular immunity are not well defined. Autologous human leukocyte antigen (HLA)-derived peptides constitute a significant proportion of the repertoire. Methods. We have investigated the response to HLA-derived peptides after allogeneic BMT using γ-interferon enzyme-linked immunospot assay (ELISPOT). We also studied the release of this γ-interferon by flow cytometry in a subgroup of responsive patients. Results. The peripheral blood mononuclear cell response was assessed by γ-interferon ELISPOT in 42 BMT recipients (21 with cGVHD) and 30 healthy donors. Thirteen of 21 patients diagnosed with cGVHD responded to at least one HLA-derived peptide compared with 1 of 21 patients without cGVHD (62% vs. 5%, P<10-4) and 1 of 30 healthy donors. In all but one patient these peptides correspond with the sequences of autologous HLA. The median single peptide-specific response in ELISPOT was 43/106 peripheral blood mononuclear cells. In a subgroup studied by flow cytometry, γ-interferon production to individual peptides occurred in 0.04% to 0.18% of CD4+ T lymphocytes. Conclusion. These observations identify HLA-derived peptides as targets of a cellular immune response in cGVHD.

Original languageEnglish (US)
Pages (from-to)555-563
Number of pages9
JournalTransplantation
Volume90
Issue number5
DOIs
StatePublished - Sep 15 2010

Keywords

  • HLA
  • Peptide
  • cGVHD

ASJC Scopus subject areas

  • Transplantation

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    Smith, H. J., Hanvesakul, R., Morgan, M. D., Bentall, A., Briggs, D., Clark, F., Pratt, G., Moss, P., Larché, M., & Ball, S. (2010). Chronic graft versus host disease is associated with an immune response to autologous human leukocyte antigen-derived peptides. Transplantation, 90(5), 555-563. https://doi.org/10.1097/TP.0b013e3181e86b58