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Several genes involved in the pathogenesis have been identified, with the human leukocyte antigen (HLA) system playing an essential role. However, the relationship between HLA and a cluster of hematological diseases has received little attention in China. Blood samples (n = 123913) from 43568 patients and 80345 individuals without known pathology were genotyped for HLA class I and II using sequencing-based typing. We discovered that HLA-A*11:01, B*40:01, C*01:02, DQB1*03:01, and DRB1*09:01 were prevalent in China. Furthermore, three high-frequency alleles (DQB1*03:01, DQB1*06:02, and DRB1*15:01) were found to be hazardous in malignant hematologic diseases when compared to controls. In addition, for benign hematologic disorders, 7 high-frequency risk alleles (A*01:01, B*46:01, C*01:02, DQB1*03:03, DQB1*05:02, DRB1*09:01, and DRB1*14:54) and 8 high-frequency susceptible genotypes (A*11:01-A*11:01, B*46:01-B*58:01, B*46:01-B*46:01, C*01:02-C*03:04, DQB1*03:01-DQB1*05:02, DQB1*03:03-DQB1*06:01, DRB1*09:01-DRB1*15:01, and DRB1*14:54-DRB1*15:01) were observed. To summarize, our findings indicate the association between HLA alleles/genotypes and a variety of hematological disorders, which is critical for disease surveillance. [ABSTRACT FROM AUTHOR]

Post-transplantation cyclophosphamide (PTCy) can reduce the incidence of graft versus host disease (GVHD) and this intervention is often applied on adults with hematologic malignancy. However, the high relapse rate hinders the development of the intervention and data of PTCy used on children with hematologic malignancy remains limited. In order to overcome issue of high relapse rate in PTCy treatment, we used fludarabine (Flu), enhanced dose of cytarabine (Ara-C, 9 g/m2), busulfan (Bu), Cy, anti-thymocyte globulin (ATG) combined with PTCy for an intensified conditioning regimen. A total of 22 children with acute leukemia received intensified PTCy conditioning regimen (PTCy intensified group). We matched with 18 children who received modified Bu-Cy and ATG conditioning regimen in the same period (ATG group). The two-year cumulative incidences of grade II–IV acute GVHD was significantly lower in PTCy intensified group (13.6 ± 7.7% vs 38.9 ± 11.5%, P = 0.048). Two-year GVHD-free relapse free survival (GRFS) in PTCy seems to be better among the increment group despite not being significant (63.3 ± 10.3% vs 35.4 ± 11.9%, P = 0.092). The positive rate of minimal residual disease after transplantation was significantly lower than that before transplantation (20.0% vs 2.5%, P = 0.029). In conclusion, ATG and PTCy combined with Flu-based increased intensity conditioning regimen is effective for acute leukemia in children. It could reduce GVHD rate significantly and potentially improve GRFS. [ABSTRACT FROM AUTHOR]

Objective: HLA-C*15:29 is a low-frequency allele in the human leukocyte antigen (HLA)-C locus. The aim of this study is to confirm the ethnicity of C*15:29 and to deduce a probable HLA haplotype in association with C*15:29 in Taiwanese population. Materials and Methods: A total of 12,534 healthy unrelated Taiwanese individuals were tested for HLA using a sequence-based typing method. The DNA material was subjected to HLA genotyping for the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci using a commercial polymerase chain reaction–sequencing-based typing kit as per the manufacturer's protocols. Results: The DNA sequence of C*15:29 is identical to C*15:02:01:01 in exons 1, 2, 3, 4, 5, and 6 except for residues 420 and 1034 where A and G of C*15:02:01:01 are substituted by C and A in C*15:29, respectively. The nucleotide substitutions introduce two amino acid replacements at residues 116 and 321 where leucine (L) and cysteine (C) of C*15:02:01:01 are replaced by phenylalanine (F) and tyrosine (Y) in C*15:29, respectively. A probable HLA haplotype associated with C*15:29 in Taiwanese was deduced as A*29:01-B*07:05-C*15:29-DRB1*10:01-DQB1*05:01. The frequency of C*15:29 is estimated at about 0.064%. Conclusion: Information on the ethnicity and distribution of C*15:29 and its deduced probable HLA haplotype is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Objective: HLA-B*40:247 is a low incidence allele in the HLA-B locus. The aim of this study is to confirm the ethnicity of B*40:247 and its deduced probable HLA- associated haplotype in Taiwanese individuals. Materials and Methods: A total of 2,329 unrelated Taiwanese individuals and 66,212 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. We confirmed the low incidence allele B*40:247 in Taiwanese. Polymerase chain reaction was performed to amplify exons 2, 3 and 4 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the *BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. Results: The DNA sequence of B*40:247 is identical to B*40:01:01 in exons 2, 3 and 4 except for residue 853, where G of B*40:01:01 is changed to A in B*40:247 (codon 261, GTA->ATA). The nucleotide replacement causes a one amino acid change at codon 261 where V (valine) of B*40:01:01 is replaced by I (isoleucine) in B*40:247. We deduced the probable HLA haplotype associated with B*40:247 in Taiwanese to be HLA-A*24:02-B*40:247-C*03:04-DRB1*16:02. Conclusion: Information on the ethnicity and distribution of B*40:247 and its deduced probable HLA haplotype in association with the low incidence allele is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Objective: Human leukocyte antigen (HLA)-DRB1*15:140 is a low-frequency allele in the HLA-DRB1 locus. The aim of this study is to confirm the ethnicity of DRB1*15:140 and to deduce a probable HLA-DRB1*15:140-associated HLA haplotype in Taiwanese individuals. Materials and Methods: A total of 1815 healthy unrelated Taiwanese individuals and 14,562 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exons 1 and 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. Results: The DNA sequence of HLA-DRB1*15:140 is identical to DRB1*15:02:01:01 in exons 1 and 2, except at residue 91 of DRB1*15:02:01:01 where a G in DRB1*15:02:01:01 is replaced by an A in DRB1*15:140 (codon 2; GAC->AAC). The nucleotide substitution in exon 1 introduces a one amino acid substitution at residue 2 where an aspartic acid (D) in DRB1*15:02:01:01 is replaced by an asparagine (N) in DRB1*15:140. We deduced the probable HLA haplotype associated with DRB1*15:140 in Taiwanese to be HLA-A*33:03-B*58:01-DRB1*15:140. Conclusion: Information on the ethnicity and distribution of DRB1*15:140 and its deduced probable HLA haplotype in association with the low-incidence allele is of value for HLA-testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Objective: Human leukocyte antigen (HLA) DRB1*04:36 is a low-frequency HLA-DRB1 allele. The aim here is to report the ethnicity of DRB1*04:36 and its associated HLA haplotypes among Taiwanese individuals. Materials and Methods: A sequence-based typing method was employed to confirm this low incidence allele. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits and the manufacturer's protocols. One group of unrelated blood donors used in this study consists of randomized individuals with Taiwanese ethnicity who participate in the Tzu Chi Bone Marrow Donor Registry and the other group are randomized unrelated individuals from mainland China. The family members in the family part of the study are volunteer blood donors. Results: In exon 2, the DNA sequence of DRB1*04:36 is identical to DRB1*04:03:01 except for a nucleotide segment from residue 286 to residue 308. The nucleotide segment from residue 286 to residue 308, incidentally, is identical to that of DRB1*11:01:01:01. These observations suggest that DRB1*04:36 may have been derived through a gene recombination event involving DRB1*04:03:01 and DRB1*11:01:01:01. Our family study indicated that the HLA haplotype in association with DRB1*04:36 can be deduced to be A*24:02-B*39:01-DRB1*04:36. A randomized population study using Taiwanese suggests that additional DRB1*04:36 associated HLA haplotypes seem to exist. Conclusion: The information on the ethnicity of the DRB1**04:36 allele, and the deduced probable HLA haplotypes associated with the low incidence DRB1*04:36 allele that we report here, is of value to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to aid the creation of strategy for finding compatible donors who are part of unrelated bone marrow donor registries when a patient carries this uncommon HLA allele.

Objective: HLA-A*11:256Q and HLA-A*02:621 are two low-frequency HLA-A alleles. The aim here is to report the ethnicity of A*11:256Q and A*02:621 and associated human leukocyte antigen (HLA) haplotypes among Taiwanese individuals. Materials and Methods: HLA data from randomized Taiwanese registered in the Tzu Chi Stem Cells Centre and China Shanghai Tissuebank Diagnostics were analyzed. HLA typing of the donors was carried out using a sequence-based typing method to confirm the two low-incidence alleles. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits and the manufacturer's protocols. Exon 1 and exons 4-8 of the A*11:256Q allele were also sequenced and analyzed. Results: The Taiwanese ethnicity for both A*11:256Q and A*02:621 alleles was confirmed in this study. Further, the DNA sequence of A* 11:256Q was confirmed to be identical to A*11:02:01from exon 1 to exon 8 except for the residues from 409 to 417 where a segment of nine nucleotides (TACCGGCAG) is deleted in A*11:256Q. The HLA haplotype associated with A*11:256Q was deduced as A*11:256Q-B*27-DRB1*12. In exons 2 and 3, the DNA sequence of A*02:621 is identical to A*02:01:01:01 except at residue 169 where T of A*02:01:01:01 is replaced by C in A*02:621 (at codon 33; TTC->CTC). The HLA haplotype in association with A*02:621 was deduced as A*02:621-B*15:18-DRB1*12:02. Conclusion: The information on the ethnicity of the A*11:256Q and A*02:621 alleles and the deduced probable HLA haplotypes associated with the two low-incidence alleles reported here are valuable to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to aid in finding compatible donors in unrelated bone marrow donor registries when a patient carries these uncommon HLA alleles.

The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59–0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59–0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41–0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58–0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease. [ABSTRACT FROM AUTHOR]

HLA‐A*68:302 differs from HLA‐A*68:01:02:01 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]

HLA‐B*44:03:67 differs from HLA‐B*44:03:02:01 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]

HLA‐C*06:02:105 differs from HLA‐C*06:02:01:01 by one nucleotide in exon 1. [ABSTRACT FROM AUTHOR]

HLA‐DPB1*05:01:18 differs from HLA‐DPB1*05:01:01:01 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]

HLA‐A*24:02:160 differs from HLA‐A*24:02:01:01 by one nucleotide in exon 3. [ABSTRACT FROM AUTHOR]

HLA‐A*02:07:22 differs from HLA‐A*02:07:01:01 by one nucleotide in exon 3. [ABSTRACT FROM AUTHOR]

HLA‐C*04:490 differs from HLA‐C*04:01:01:01 by one nucleotide in exon 3. [ABSTRACT FROM AUTHOR]

HLA‐DQB1*03:03:29 differs from HLA‐DQB1*03:03:02:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐DRB1*14:07:03 differs from HLA‐DRB1*14:07:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐B*15:644 differs from HLA‐B*15:17:01:02 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]

HLA‐DQB1*04:93 differs from HLA‐DQB1*04:01:01:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐DPB1*02:02:07 differs from HLA‐DPB1*02:02:01:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

The triallelic pattern of short tandem repeat (STR) is rare; especially, the case where this pattern exists at 4 loci has not been reported. Here, we report the type 1 triallelic patterns at D5S818, D18S51, D6S1043, and FGA from a Chinese family, which were observed during our routine chimerism assays. Before hematopoietic stem cell transplantation, the blood sample of the certain patient was analyzed by performing chimerism analysis. A preliminary STR analysis was also performed on the samples of the patient's parents. STR signal data illustrated that the sum of the peak chart areas of the two types inherited from the father was basically the same as that of the mother, belonging to the type 1 triallelic pattern. In addition, the patient's elder sister's STR result appeared to be normal. Altogether, we presented a pedigree, in which the triallelic pattern was linked by inheritance in the family. This is the first reported case of the triallelic pattern at D5S818, D18S51, D6S1043, and FGA all around the world. We hope that in the future there will be any tools to achieve accurate verification against this possibility. [ABSTRACT FROM AUTHOR]

HLA‐DRB1*14:246 differs from HLA‐DRB1*14:18 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐DPB1*1352:01 differs from HLA‐DPB1*02:01:02:01 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]

HLA‐B*15:638 differs from HLA‐B*15:01:01:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐C*06:02:102 differs from HLA‐C*06:02:01:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

Mastering the SNP content in the HLA region can be based on it to judiciously select unrelated donor stem cells with preferable MHC matching to lower postoperative complications. Herein, quantitative PCR‐based primers and probes were designed for 10 transplants outcome‐associated SNP loci with two‐allelic polymorphism, and then a new detection system ("HLA‐10‐SNP") was established. Compared with Sanger sequencing, its accuracy has been proven to reach 100%. Additionally, fluorescent PCR typing of 10 important SNPs via this system expressed excellent repeatability (sensitivity, 20 ng). Overall, the new system achieves single‐sample classification precision and easily distinguishable results, equipped with the advantages of simple, rapid, accurate, and effective, promising to acquire widespread popularization and application in clinical settings. [ABSTRACT FROM AUTHOR]

HLA‐C*04:01:152 differs from HLA‐C*04:01:01:01 by one nucleotide in exon 1. [ABSTRACT FROM AUTHOR]

HLA‐A*30:01:24 differs from HLA‐A*30:01:01:01 by one nucleotide in exon 3. [ABSTRACT FROM AUTHOR]

HLA‐B*40:536N differs from HLA‐B*40:03:01:01 by one nucleotide in exon 3. [ABSTRACT FROM AUTHOR]

HLA‐B*51:381 differs from HLA‐B*51:01:01:01 by one nucleotide in exon 5. [ABSTRACT FROM AUTHOR]

HLA‐A*02:07:23 differs from HLA‐A*02:07:01:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

The killer cell immunoglobulin-like receptor (KIR), which mediates the killing function of NK cells, is an attractive candidate for adoptive cellular therapy. The ethnic distribution for China provides a unique opportunity to investigate KIR gene distribution. The aim of this study was to explore the relationship between population history and the rapidly evolving KIR genetic diversity. 8050 Chinese donors from 184 hospitals were included to analyse frequency, haplotype, and B-content data of 16 KIR genes, by PCR-SSP for KIR genotyping. KIR gene carrier frequencies were found similar to those observed in other studies on Han, but different from Thais, Japanese, Africans, and populations of West Eurasian ancestry. High-frequency KIR genotype profiles found in the present population were consistent with other studies on Han populations but different from those conducted on other cohorts. The majority of our cohort carried group A KIR gene motifs. Additionally, populations with similar geographic locations in China were shown clustered together, while Hainan and Xinjiang provinces were slightly separated from these. The distribution of KIR genes varies by geographic region, and different ethnic groups may be a confounding factor of KIR diversity. [ABSTRACT FROM AUTHOR]

HLA‐DRB1*14:251 differs from HLA‐DRB1*14:126:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐C*03:621 differs from HLA‐C*03:04:01:01 by one nucleotide in exon 1. [ABSTRACT FROM AUTHOR]

HLA‐C*12:368 differs from HLA‐C*12:03:01:01 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]

HLA‐A*24:582 differs from HLA‐A*24:02:01:01 by one nucleotide in exon 1. [ABSTRACT FROM AUTHOR]

HLA‐C*15:02:58 differs from HLA‐C*15:02:01:01 by one nucleotide in exon 1. [ABSTRACT FROM AUTHOR]

HLA‐B*48:01:11 differs from HLA‐B*48:01:01:01 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]

HLA‐A*24:561:02 differs from HLA‐A*24:02:01:01 by one nucleotide in exon 3. [ABSTRACT FROM AUTHOR]

HLA‐C*07:1029 differs from HLA‐C*07:02:01:01 by one nucleotide in exon 5. [ABSTRACT FROM AUTHOR]

HLA‐DQB1*06:208:02 differs from HLA‐DQB1*06:02:02 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐B*13:01:21 differs from HLA‐B*13:01:01:01 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐A*02:1075 differs from HLA‐A*02:07:01:01 by one nucleotide in exon 5. [ABSTRACT FROM AUTHOR]

HLA‐A*24:02:159 differs from HLA‐A*24:02:01:01 by one nucleotide in exon 3. [ABSTRACT FROM AUTHOR]

HLA‐C*01:239 differs from HLA‐C*01:02:01:01 by one nucleotide in exon 4. [ABSTRACT FROM AUTHOR]