ABSTRACT
<p><b>OBJECTIVE</b>To analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients.</p><p><b>METHODS</b>HLA high-resolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out.</p><p><b>RESULTS</b>Forty-four HLA-A alleles were detected, and among them the frequencies of A*1101, A*2402, A*0201, A*0207, A*3303, A*0206 and A*3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and the frequencies of B*4001, B*4601, B*5801, B*1302 and B*5101 exceeded 0.05, and accounted for 43.0% of total. There were 44 HLA-Cw alleles, among them the frequencies of Cw*0702, Cw*0102, Cw*0304, Cw*0801, Cw*0602, Cw*0303, Cw*0302 and Cw*0401 exceeded 0.05, and were 80.3% of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1*0901, DRB1*1501, DRB1*1202, DRB1*0803, DRB1*0701, DRB1*0405, DRB1*0301 and DRB1*1101 exceeded 0.05, and were 70.1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1*0301, DQB1*0303, DQB1*0601, DQB1*0602, DQB1*0202, DQB1*0302, DQB1*0401, DQB1*0502 and DQB1*0201 exceeded 0.05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P > 0.05); but HLA-Cw and HLA-DQB1 loci did not (P < 0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24.6% of recipients found single HLA allele mismatched donors (9/10); 26.3% of recipients had two HLA alleles mismatched donors (8/10).</p><p><b>CONCLUSION</b>The characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.</p>
Subject(s)
Humans , China , Ethnology , Gene Frequency , Genetics, Population , HLA-A Antigens , Genetics , HLA-B Antigens , Genetics , HLA-C Antigens , Genetics , HLA-D Antigens , Genetics , HLA-DQ Antigens , Genetics , HLA-DQ beta-Chains , HLA-DR Antigens , Genetics , HLA-DRB1 Chains , Hematopoietic Stem Cell Transplantation , Histocompatibility Antigens Class I , Genetics , Histocompatibility Testing , Tissue DonorsABSTRACT
<p><b>OBJECTIVE</b>To study the biological function of killer cell immunoglobulin-like receptor (KIR) and the role of donor inhibitory KIR and recipient genetic background in HLA matched unrelated hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>HLA genotype of 51 patients (ALL 18 cases, CML 15 cases, AML 10 cases and others 8 cases) and their respective matched unrelated donors from Database of China Marrow Registration was determined by polymerase chain reaction sequence oligonucleotide probes (PCR-SSOP) and sequence specific primers (PCR-SSP). The KIR genotype was determined by PCR-SSP.</p><p><b>RESULTS</b>All the patients and the donors expressed KIR2DL1, KIR2DL2/L3, KIR2DL4, KIR3DL2 and KIR3DL3. 96.7% individuals expressed KIR3DL1. Among them, 21.57% of KIR was completely identical, while 78.43% was not. Of the non-identical KIRs, 25.49% were the recipient's KIR genotype containing the donor's ones, and 27.45% was the donor's containing the recipient's. 74.62% of donor's KIR2DL1 lacked recipient's C2 ligand, 5.91% of donor's KIR2DL2/L3 lacked recipient's C1 ligand, 19.74% of donor's KIR3DL1 lacked recipient's Bw4 ligand and 54.91% of donor's KIR3DL2 lacked recipient's A3, A11 ligand.</p><p><b>CONCLUSION</b>KIR genotype and HLA class I antigen are inherited independently. KIR2DLI and KIR3DL2 of donors may cause alloreactivity of NK cell. The mismatch of KIR/HLA in donor-recipient plays a very important role in matched unrelated allo-HSCT. The outcome of HSCT can be better predicted by the model of the presence of KIRs on the donor' sNK cells and the absence of corresponding KIR ligand in the recipient's HLA.</p>
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Gene Frequency , Genotype , HLA Antigens , Genetics , Hematopoietic Stem Cell Transplantation , Killer Cells, Natural , Allergy and Immunology , Receptors, KIR , Genetics , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of HLA-Cw on haploidentical hematopoietic stem cell transplantation (HHSCT) without T-cell depletion.</p><p><b>METHODS</b>HLA-Cw were detected with PCR-SSP, the clinical data of 21 cases of haploidentical hematopoietic stem cell transplantation, including 8 standard risk and 13 high risk cases from July 2002 to March 2006 were summarized, and the effect of HLA-Cw in HHSCT was analyzed.</p><p><b>RESULTS</b>Twenty patients achieved sustained, full-donor-type engraftment. The HLA-Cw matched and mismatched groups attained neutrophil recovery at a median of 12 days and 13 days, and platelet recovery to more than 20 x 10(9)/L at a median of 20 days and 23 days respectively (P > 0.05). The cumulative incidences of grades II-IV acute GVHD were 76.9% in HLA-Cw matched group and 14.3% in the mismatched group(P < 0.05). The incidences of chronic GVHD were 85.7% in HLA-Cw matched group and 57.1% in the mismatched group(P > 0.05). The 28 months disease-free survival probabilities were 49.0% in HLA-Cw matched group, and 85.7% in the mismatched group (P > 0.05). The Karnofsky score of survival patients was over 90%.</p><p><b>CONCLUSION</b>HLA-Cw mismatched in donor and recipient of HHSCT is beneficial for reducing II-IV aGVHD, and being in favor of long term survival.</p>