Association between human leukocyte antigens and graft-versus-host disease occurrence after allogenic hematopoietic stem cell transplantation
Keywords:
Graft vs host disease, Histocompatibility antigens, Hematopoietic stem cells, Polymorphism, genetic, TransplantsAbstract
CONTEXT AND OBJECTIVE: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. DESIGN AND SETTING: Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). METHODS: The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. RESULTS: Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). CONCLUSION: This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.
Downloads
References
Dickinson AM, Charron D. Non-HLAimmunogeneticsinhematopoietic stem cell transplantation. Curr Opin Immunol. 2005;17(5):517-25.
Charron D. Immunogenetics today: HLA, MHC and much more. Curr Opin Immunol. 2005;17(5):493-7.
Mohyeddin Bonab M, Alimoghaddam K, Vatandoust S, et al. Are HLA antigens a risk factor for acute GVHD in thalassemic patients
receiving HLA-identical stem cell transplantation? Transplant Proc. 2004;36(10):3190-3.
Battiwalla M, Hahn T, Radovic M, et al. Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence. Blood. 2006;107(5):1970-3.
Storb R, Prentice RL, Hansen JA, Thomas ED. Association between HLA-B antigens and acute graft-versus-host disease. Lancet. 1983;2(8354):816-9.
Clark RE, Hermans J, Madrigal A, et al. HLA-A3 increases and HLA- DR1 decreases the risk of acute graft-versus-host disease after HLA-matched sibling bone marrow transplantation for chronic myelogenous leukaemia. Br J Haematol. 2001;114(1):36-41.
Weisdorf D, Hakke R, Blazar B, et al. Risk factors for acute graft-versus- host disease in histocompatible donor bone marrow transplantation. Transplantation. 1991;51(6):1197-203.
Bross DS, Tutschka PJ, Farmer ER, et al. Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow. Blood. 1984;63(6):1265-70.
Remberger M, Persson U, Hauzenberger D, Ringdén O. An association between human leucocyte antigen alleles and acute and chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2002;119(3):751-9.
Ghavamzadeh A, Alimoghaddam K, Behrouzan O, et al. HLA and risk of acute graft versus host disease in allogenic bone marrow transplantation from an HLA-identical sibling. Arch Irn Med. 2002;5(1):16-20. Available from: http://www.ams.ac.ir/AIM/0251/ aim025116.htm. Accessed in 2011 (Nov 22).
Adams KM, Holmberg LA, Leisenring W, et al. Risk factors for syngeneic graft-versus-host disease after adult hematopoietic cell transplantation. Blood. 2004;104(6):1894-7.
Stern M, Passweg J, Tiercy JM, et al. Human leukocyte antigen DR15 is associated with reduced relapse rate and improved survival after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2006;12(11):1169-75.
Petersdorf EW, Malkki M. Genetics of risk factors for graft-versus-host disease. Semin Hematol. 2006;43(1):11-23.
Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft- versus-host disease in human recipients of marrow from HL-A- matched sibling donors. Transplantation. 1974;18(4):295-304.
Atkinson K, Horowitz MM, Gale RP, et al. Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease. Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant. 1989;4(3):247-54.
Visentainer JE, Lieber SR, Persoli LB, et al. Serum cytokine levels and acute graft-versus-host disease after HLA-identical hematopoietic stem cell transplantation. Exp Hematol. 2003;31(11):1044-50.
Vigorito AC, Azevedo WM, Marques JF, et al. A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies. Bone Marrow Transplant. 1998;22(12):1145-51.
Lin MT, Storer B, Martin PJ, et al. Relation of an interleukin-
promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med. 2003;349(23):2201-10.
Laguila Visentainer JE, Lieber SR, Lopes Persoli LB, et al. Relationship between cytokine gene polymorphisms and graft-versus-host disease after allogeneic stem cell transplantation in a Brazilian population. Cytokine. 2005;32(3-4):171-7.
Hsu KC, Keever-Taylor CA, Wilton A, et al. Improved outcome in HLA- identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood. 2005;105(12):4878-84.
Viel DO, Tsuneto LT, Sossai CR, et al. IL2 and TNFA gene polymorphisms and the risk of graft-versus-host disease after allogeneic haematopoietic stem cell transplantation. Scand J Immunol. 2007;66(6):703-10.
Azarpira N, Ramzi M, Aghdaie MH, Darai M, Geramizadeh B. Interleukin- 10 gene polymorphism in bone marrow transplant recipients. Exp Clin Transplant. 2008;6(1):74-9.
Schellekens J, Rozemuller EH, Petersen EJ, et al. Activating KIRs exert a crucial role on relapse and overall survival after HLA-identical sibling transplantation. Mol Immunol. 2008;45(8):2255-61.
Visentainer JEL, Sell AM, Franceschi DA, Lieber SR, Souza CA. Importância de polimorfismos de genes reguladores de citocinas em transplantes de células progenitoras hematopoiéticas [Importance of regulatory cytokine gene polymorphisms in hematopoietic stem cell transplantation]. RBCF Rev Bras Ciênc Farm (Impr). 2008;44(4):739-48.
