PMID- 20616766 OWN - NLM STAT- MEDLINE DCOM- 20101027 LR - 20211028 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 90 IP - 5 DP - 2010 Sep 15 TI - Chronic graft versus host disease is associated with an immune response to autologous human leukocyte antigen-derived peptides. PG - 555-63 LID - 10.1097/TP.0b013e3181e86b58 [doi] AB - 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 gamma-interferon enzyme-linked immunospot assay (ELISPOT). We also studied the release of this gamma-interferon by flow cytometry in a subgroup of responsive patients. RESULTS: The peripheral blood mononuclear cell response was assessed by gamma-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) 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 43/10 peripheral blood mononuclear cells. In a subgroup studied by flow cytometry, gamma-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. FAU - Smith, Helen J AU - Smith HJ AD - Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, UK & School of Immunity, Infection and Inflammation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. FAU - Hanvesakul, Rajesh AU - Hanvesakul R FAU - Morgan, Matthew D AU - Morgan MD FAU - Bentall, Andrew AU - Bentall A FAU - Briggs, David AU - Briggs D FAU - Clark, Fiona AU - Clark F FAU - Pratt, Guy AU - Pratt G FAU - Moss, Paul AU - Moss P FAU - Larche, Mark AU - Larche M FAU - Ball, Simon AU - Ball S LA - eng GR - G9901249/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Bone Marrow Transplantation/*immunology MH - Female MH - Graft vs Host Disease/etiology/*immunology MH - HLA Antigens/*immunology MH - Histocompatibility Antigens Class I/immunology MH - Humans MH - Immunity, Cellular MH - Immunity, Humoral MH - Immunophenotyping/methods MH - Interferon-gamma/biosynthesis/blood MH - Leukemia/surgery MH - Lymphocytes/immunology MH - Male MH - Transplantation, Homologous/immunology EDAT- 2010/07/10 06:00 MHDA- 2010/10/28 06:00 CRDT- 2010/07/10 06:00 PHST- 2010/07/10 06:00 [entrez] PHST- 2010/07/10 06:00 [pubmed] PHST- 2010/10/28 06:00 [medline] AID - 10.1097/TP.0b013e3181e86b58 [doi] PST - ppublish SO - Transplantation. 2010 Sep 15;90(5):555-63. doi: 10.1097/TP.0b013e3181e86b58.