Degree of predicted minor histocompatibility antigen mismatch correlates with poorer clinical outcomes in nonmyeloablative allogeneic hematopoietic cell transplantation

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Malene Erup LarsenLars Vindelov

Abstract

In fully HLA-matched allogeneic hematopoietic cell transplantation (HCT), the main mechanism of the beneficial graft-versus-tumor (GVT) effect and of detrimental graft-versus-host disease (GVHD) is believed to be caused by donor cytotoxic T cells directed against disparate recipient minor histocompatibility antigens (miHAs). The most common origin of disparate miHAs is nonsynonymous single nucleotide polymorphism (nsSNP) differences between donors and patients. To date, only some 30 miHAs have been identified and registered, but considering the many different HLA types in the human population, as well as all the possible nsSNP differences between any 2 individuals, it is likely that many miHAs have yet to be discovered. The objective of the current study was to predict novel HLA-A- and HLA-B-restricted miHAs in a cohort of patients treated with nonmyeloablative conditioning allogeneic HCT (matched related donor, n = 70; matched unrelated donor, n = 56) for a hematologic malignancy. Initially, the cohort was genotyped for 53 nsSNPs in 11 known miHA source proteins. Twenty-three nsSNPs within 6 miHA source proteins showed variation in the graft-versus-host (GVH) direction. No correlation between the number of disparate nsSNPs and...Continue Reading

References

Apr 7, 1977·Nature·Els GoulmyJon J van Rood
Jan 20, 1999·The Journal of Experimental Medicine·Harry DolstraElly van de Wiel-van Kemenade
Dec 11, 1999·Nucleic Acids Research·E M SmigielskiS T Sherry
Jan 11, 2000·Nucleic Acids Research·J RobinsonS G Marsh
Oct 24, 2001·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·F C GrumetR S Negrin
Dec 21, 2002·Immunological Reviews·Derry RoopenianAaron Brown
Jan 10, 2003·Nucleic Acids Research·James RobinsonSteven G E Marsh
Feb 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·W A Erik MarijtJ H Frederik Falkenburg
May 14, 2003·The Journal of Experimental Medicine·Makoto MurataStanley R Riddell
May 29, 2003·The Journal of Experimental Medicine·Yoshiki AkatsukaToshitada Takahashi
Nov 20, 2003·JAMA : the Journal of the American Medical Association·Vikas Bhushan, Robert H Collins
Dec 20, 2003·Nature·International HapMap Consortium
May 4, 2004·Nature Reviews. Cancer·Marie Bleakley, Stanley R Riddell
Dec 13, 2005·Immunogenetics·Mathias M SchulerStefan Stevanovic
Jun 23, 2006·PLoS Computational Biology·Bjoern PetersAlessandro Sette
Aug 9, 2006·International Journal of Immunogenetics·M Halling-BrownD S Moss
Sep 9, 2006·Science·Edus H WarrenBenoît J Van den Eynde
Apr 24, 2007·Best Practice & Research. Clinical Haematology·Lothar HambachEls Goulmy
Jul 6, 2007·Tissue Antigens·B KornblitPeter Garred
Jul 6, 2007·Leukemia·J H Kessler, C J M Melief
Sep 24, 2008·Blood·Michi KameiYoshiki Akatsuka
Oct 8, 2008·Nucleic Acids Research·James RobinsonSteven G E Marsh
Nov 13, 2008·Immunogenetics·Ilka HoofMorten Nielsen
Mar 14, 2009·Lancet·James L M FerraraErnst Holler
Jun 23, 2009·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Stephen SpellmanThomas M Ellis
Jul 3, 2009·Bioinformatics·David S DeLucaRainer Blasczyk

Related Concepts

Fludarabine
Graft-vs-Host Disease
Histocompatibility
Transplantation, Homologous
Vira-A
Whole-Body Irradiation
Incidence Studies
Minor Histocompatibility Antigens
Cox Proportional Hazards Models
Hemopoietic Stem Cell Transplant

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.