The human leukocyte antigen (HLA) system plays a crucial role in immune function, and HLA testing is often needed in the support of patients with cancer.
Methods
We briefly review the published literature to clarify the nomenclature of the HLA system, currently available methods for HLA testing, and commonly used HLA assays. The uses of HLA testing in pharmacogenomics, disease association, platelet transfusion support, and in the management of both solid organ and hematopoietic stem cell transplantation are also reviewed.
Results
HLA testing is commonly performed for select patient populations, including patients with cancer and in those requiring solid organ and hematopoietic stem cell transplantation.
Conclusion
Newer molecular typing methods have helped improve patient outcomes following hematopoietic stem cell transplantation.
References
1.
TerasakiP.I., McClellandJ.D.. Microdroplet assay of human serum cytotoxins.Nature.1964; 204: 998–1000.
2.
MarshS.G., AlbertE.D., BodmerW.F.. Nomenclature for factors of the HLA system, 2010.Tissue Antigens.2010; 75(4): 291–455.
3.
Anthony Nolan Research Institute.Nomenclature for factors of the HLA system.http://hla.alleles.org. Accessed October 30, 2014.
GatanagaH., HondaH., OkaS.. Pharmacogenetic information derived from analysis of HLA alleles.Pharmacogenomics.2008; 9(2): 207–214.
10.
ShearN.H., MilpiedB., BruynzeelD.P.. A review of drug patch testing and implications for HIV clinicians.AIDS.2008; 22(9): 999–1007.
11.
HungS.I., ChungW.H., LiouL.B.. HLA-B∗5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol.Proc Natl Acad Sci U S A.2005; 102(11): 4134–4139.
12.
ChungW.H., HungS.I., HongH.S.. Medical genetics: a marker for Stevens-Johnson syndrome.Nature.2004; 428(6982): 486.
13.
DalyA.K., DonaldsonP.T., BhatnagarP.; DILIGEN Study; International SAE Consortium. HLA-B∗5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin.Nat Genet.2009; 41(7): 816–819.
14.
KimmelS.E., FrenchB., KasnerS.E.; COAG Investigators. A pharmacogenetic versus a clinical algorithm for warfarin dosing.N Engl J Med.2013; 369(24): 2283–2293.
15.
VerhoefT.I., RagiaG., de BoerA.; EU-PACT Group. A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon.N Engl J Med.2013; 369(24): 2304–2312.
16.
AlcocebaM., SebastianE., MarinL.. HLA specificities are related to development and prognosis of diffuse large B-cell lymphoma.Blood.2013; 122(8): 1448–1454.
17.
AmielJ.L.. Study of the leukocyte phenotypes in Hodgkin's disease. In: CurtoniE.S., MattiuzP.I., TosiR.M., eds. Histocompatibility Testing.Munksgaard, Copenhagen: Consiglio Nazionale delle Ricerche;1967: 79–81.
18.
JinY.J., ShimJ.H., ChungY.H.. Relationship of HLA-DRB1 alleles with hepatocellular carcinoma development in chronic hepatitis B patients.J Clin Gastroenterol.2012; 46(5): 420–426.
19.
HayashiR., OchiaiT.. HLA type and survival in gastric cancer.Cancer Res.1986; 46(7): 3701–3703.
20.
Trial to Reduce Alloimmunization to Platelets Study Group.Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions.N Engl J Med.1997; 337(26): 1861–1869.
21.
TriulziD.J., KleinmanS., KakaiyaR.M.. The effect of previous pregnancy and transfusion on HLA alloimmunization in blood donors: implications for a transfusion-related acute lung injury risk reduction strategy.Transfusion.2009; 49(9): 1825–1835.
22.
O'ConnellB., LeeE.J., SchifferC.A.. The value of 10-minute posttransfusion platelet counts.Transfusion.1988; 28(1): 66–67.
23.
DavisK.B., SlichterS.J., CorashL.. Corrected count increment and percent platelet recovery as measures of posttransfusion platelet response: problems and a solution.Transfusion.1999; 39(6): 586–592.
24.
SpellmanS.R., EapenM., LoganB.R.; National Marrow Donor Program; Center for International Blood and Marrow Transplant Research. A perspective on the selection of unrelated donors and cord blood units for transplantation.Blood.2012; 120(2): 259–265.
25.
PetersdorfE.W.. Risk assessment in haematopoietic stem cell transplantation: histocompatibility.Best Pract Res Clin Haematol.2007; 20(2): 155–170.
26.
PetersdorfE.W., HansenJ.A., MartinP.J.. Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation.N Engl J Med.2001; 345(25): 1794–1800.
27.
CrocchioloR., CiceriF., FleischhauerK.. HLA matching affects clinical outcome of adult patients undergoing haematopoietic SCT from unrelated donors: a study from the Gruppo Italiano Trapianto di Midollo Osseo and Italian Bone Marrow Donor Registry.Bone Marrow Transplant.2009; 44(9): 571–577.
28.
GragertL., EapenM., WilliamsE.. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry.N Engl J Med.2014; 371(4): 339–348.
29.
KekreN., AntinJ.H.. Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist.Blood.2014; 124(3): 334–343.
30.
LeeS.J., KleinJ., HaagensonM.. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation.Blood.2007; 110(13): 4576–4583.
31.
FlomenbergN., Baxter-LoweL.A., ConferD.. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome.Blood.2004; 104(7): 1923–1930.
32.
PetersdorfE.W., AnasettiC., MartinP.J.. Limits of HLA mismatching in unrelated hematopoietic cell transplantation.Blood.2004; 104(9): 2976–2980.
33.
PidalaJ., WangT., HaagensonM.. Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality.Blood.2013; 122(22): 3651–3658.
34.
Fernandez-ViñaM.A., WangT., LeeS.J.. Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation.Blood.2014; 123(8): 1270–1278.
35.
HarkenseeC., OkaA., OnizukaM.. Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation: an exploration study.Blood.2012; 119(26): 6365–6372.
36.
MorishimaS., OgawaS., MatsubaraA.; Japan Marrow Donor Program. Impact of highly conserved HLA haplotype on acute graft-versus-host disease.Blood.2010; 115(23): 4664–4670.
37.
McCulloughJ., PerkinsH.A., HansenJ.. The National Marrow Donor Program with emphasis on the early years.Transfusion.2006; 46(7): 1248–1255.
38.
AppelbaumF.R.. Pursuing the goal of a donor for everyone in need.N Engl J Med.2012; 367(16): 1555–1556.
39.
BallenK.K., GluckmanE., BroxmeyerH.E.. Umbilical cord blood transplantation: the first 25 years and beyond.Blood.2013; 122(4): 491–498.
40.
BarkerJ.N., ByamC., ScaradavouA.. How I treat: the selection and acquisition of unrelated cord blood grafts.Blood.2011; 117(8): 2332–2339.
41.
EapenM., KleinJ.P., SanzG.F.; Eurocord-European Group for Blood and Marrow Transplantation; Netcord; Center for International Blood and Marrow Transplant Research. Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis.Lancet Oncol.2011; 12(13): 1214–1221.
42.
EapenM., KleinJ.P., RuggeriA.; Center for International Blood and Marrow Transplant Research, Netcord, Eurocord, and the European Group for Blood and Marrow Transplantation. Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy.Blood.2014; 123(1): 133–140.
43.
WoolfreyA., KleinJ.P., HaagensonM.. HLA-C antigen mismatch is associated with worse outcome in unrelated donor peripheral blood stem cell transplantation.Biol Blood Marrow Transplant.2011; 17(6): 885–892.
44.
ZinoE., FrumentoG., MarktelS.. A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation.Blood.2004; 103(4): 1417–1424.
45.
FleischhauerK., ShawB.E., GooleyT.; International Histocompatibility Working Group in Hematopoietic Cell Transplantation. Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study.Lancet Oncol.2012; 13(4): 366–374.
46.
AnasettiC., AmosD., BeattyP.G.. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma.N Engl J Med.1989; 320(4): 197–204.
47.
YoshiharaS., TaniguchiK., OgawaH.. The role of HLA antibodies in allogeneic SCT: is the ‘type-and-screen’ strategy necessary not only for blood type but also for HLA?Bone Marrow Transplant.2012; 47(12): 1499–1506.
48.
SpellmanS., BrayR., Rosen-BronsonS.. The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure.Blood.2010; 115(13): 2704–2708.
49.
RochaV., SpellmanS., ZhangM.J.; Eurocord-European Blood and Marrow Transplant Group and the Center for International Blood and Marrow Transplant Research. Effect of HLA-matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for hematologic malignancy.Biol Blood Marrow Transplant.2012; 18(12): 1890–1896.
50.
van RoodJ.J., StevensC.E., SmitsJ.. Reexposure of cord blood to noninherited maternal HLA antigens improves transplant outcome in hematological malignancies.Proc Natl Acad Sci U S A.2009; 106(47): 19952–19957.
51.
KärreK.. Immunology. A perfect mismatch.Science.2002; 295(5562): 2029–2031.
52.
ParhamP.. MHC class I molecules and KIRs in human history, health and survival.Nat Rev Immunol.2005; 5(3): 201–214.
53.
MillerJ.S., BlazarB.R.. Control of acute myeloid leukemia relapse–dance between KIRs and HLA.N Engl J Med.2012; 367(9): 866–868.
GajewskiJ.L., JohnsonV.V., SandlerS.G.. A review of transfusion practice before, during, and after hematopoietic progenitor cell transplantation.Blood.2008; 112(8): 3036–3047.
