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To analyse the effect of HLA‐DPA1 and HLA‐DPB1 allelic mismatches on the outcomes of unrelated donor haematopoietic stem cell transplantation (URD‐HSCT), we collected 258 recipients with haematological disease who underwent HLA‐10/10 matched URD‐HSCT. HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1, ‐DRB3/4/5, ‐DQA1, ‐DPA1 and ‐DPB1 typing was performed for the donors and recipients using next‐generation sequencing (NGS) technology. After excluding 8 cases with DQA1 or DRB3/4/5 mismatches, we included 250 cases with HLA‐14/14 matching for further analysis. Our results showed that the proportion of matched DPA1 and DPB1 alleles was only 10.4% (26/250). The remaining 89.6% of donors and recipients demonstrated DPA1 or DPB1 mismatch. In the DPA1 matched and DPB1 mismatched group, accounting for 18.8% (47/250) of the cohort, DPB1*02:01/DPB1*03:01 allelic mismatches were associated with decreased 2‐year OS and increased NRM. DPB1*02:02/DPB1*05:01 and DPB1*02:01/DPB1*05:01 mismatches showed no impact on outcomes. Moreover, the specific allelic mismatches observed were consistent with the DPB1 T‐cell epitope (TCE) classification as permissive and non‐permissive. We innovatively established an analysis method for DPA1 ~ DPB1 linkage mismatch for cases with both DPA1 and DPB1 mismatched, accounting for 70% (175/250) of the total. DPA1*02:02 ~ DPB1*05:01/DPA1*02:01 ~ DPB1*17:01 linkage mismatches were associated with lower 2‐year OS, especially among AML/MDS recipients. DPA1*02:02 ~ DPB1*05:01/DPA1*01:03 ~ DPB1*02:01 linkage mismatches showed no impact on outcomes. In conclusion, applying the DPA1 ~ DPB1 linkage mismatch analysis approach can identify different types of mismatches affecting transplant outcomes and provide valuable insight for selecting optimal donors for AML/MDS and ALL recipients. [ABSTRACT FROM AUTHOR]

The focus of this study was to analyze polymorphisms in the HLA gene at 11 loci in 4845 Chinese Han populations using next‐generation sequencing methods, and to compare common and well‐documented (CWD) allelic differences between China and other CWD lists. A total of 44 DPB1 alleles, 13 DPA1 alleles, 20 DQA1 alleles and 19 DRB3/4/5 alleles were detected in this study. About 20%–50% of the CWD alleles in China differ from the American Society for Histocompatibility and Immunogenetics and European Federation for Immunogenetics (EFI) data. The revised list of HLA‐CWD alleles in the Han population will provide additional data for the update of the IMGT/HLA database and contribute to a better understanding of hematopoietic stem cell transplantation and organ transplantation. [ABSTRACT FROM AUTHOR]

With the goal of improving the population‐specific criteria to distinguish KIR genotypes and haplotypes in the region, we examined the KIR gene and haplotype data of Eastern Han based on a large population and analyzed the component genes of centromeric (Cen) and telomeric (Tel) KIR haplotype segments, which may differ in the protection they provide in hematopoietic stem cell transplantation. Samples from 598 families and 2845 unrelated individuals of Eastern Han origin were collected between 2010 and 2017. Genotyping of 17 KIR genes was performed by PCR‐SSP and SSO methods. The results showed we obtained the KIR gene distribution of the Eastern Han population. The KIR gene frequencies (GF) in the present study are similar to those observed in other studies on Han but different from other populations. We observed a total of 56 different genotypes, including 1 AA and 55 group B genotypes. The 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 populations. In the family panel, a total of 28 KIR haplotypes were identified in the segregation study. The majority of Eastern Han carried group A KIR gene motifs. Comparison of the frequencies of Cen and Tel KIR gene motifs shows that they differ from other populations. The study on the distribution of KIR genes in the population may aid in the development of a complementary population‐specific criterion to distinguish between KIR haplotypes and offer a research direction for further gene functional studies. [ABSTRACT FROM AUTHOR]

Aim: To study the distribution of the varied KIR genotypes and haplotypes in Southern Chinese Han population. Methods: We performed KIR genotyping on 1271 individuals from the south China including 102 families with 306 members and 965 unrelated individuals. The 102 families with one child and both parents were subjected for haplotype analysis. Results: The family study revealed segregation of at least 15 unique B haplotypes. The most commonly observed haplotypes in group B were B1, B2, and B3, present at a frequency of 10.05%, 6.62%, and 4.90%, respectively. Based on the combination of KIR genes, 6 centromeric and 7 telomeric gene motifs have been identified. Motif cB01 was the most frequent haplotype B specific centromeric segment while tB01 was the most frequent haplotype B specific telomeric segment. The distinct distribution of KIR haplotypes in each population may reflect the history of directional and balancing selection of different races. 43 different genotypes with at least one group B haplotype were identified (A/B or B/B). The frequencies of the KIR genotypes found in the family panel were confirmed by those found in the unrelated panel. The gene combinations of group A and B1/B2/B3 haplotype were the most frequent genotypes named as Bx1, Bx2 and Bx3, present at a frequency of 15.47%, 9.67%, and 5.56%, respectively. Conclusions: Overall, this study revealed the diversity of KIR haplotypes and genotypes in southern Chinese Han population and developed a criterion for distinguish KIR group B haplotypes/ genotypes for the population. KIR genotyping and haplotype analysis should be useful for selection of the most optimum donor grafts with favorable KIR gene content for transplants. [Copyright &y& Elsevier]

Aim: The Cylex Immuknow (IK) assay provides a rapid and quantitative assessment of T-cell-mediated immune function. Studies have shown correlations between Immuknow assay and adverse events, such as immunosuppression and low or high calcineurin inhibitor–trough levels. We investigated the correlation between IK changes and rejection or infection in kidney transplant patients, and studied the potential application of the IK assays in optimizing individual immunosuppressive therapy. Methods: Immuknow assay was used to determine dynamic intracellular ATP changes in CD4 cells in 193 samples from both 42 kidney transplant patients and 25 healthy subjects. Patients were categorized into rejection, infection, and event-free groups. The IK values were assayed and analyzed between kidney transplant patients and healthy controls. Results: Most IK values fluctuated between 200 and 599 ng/mL from pre-transplantation to 30 months post-transplantation. The mean IK values continuously increased throughout 30 months. Incidental allograft rejection patients had significantly higher IK values, compared to the event-free patients and controls. However, infection patients had significantly lower IK values. Seven days after treatment, IK values in rejection/infection patients were different compared to the values in autograft patients, and there was a significant correlation between calcineurin-inhibitor (FK506) trough levels and IK values in rejection/infection patients. Serum creatinine levels in the rejection patients were significantly higher than those in the event-free patients and C-reactive protein levels were significantly higher in the infection patients compared to the event-free patients. Conclusions: The IK assay combined with other biomarkers can be used to identify kidney transplant patients at high risk of rejection and infection. [Copyright &y& Elsevier]

Aim: Human Leukocyte Antigens (HLA), which is extremely polymorphic, plays an important role in stem cell transplantation. The Chinese Han comprise a large population of approximate 1.3 billion with diverse HLA alleles need to be characterized. Methods: Data from 3296 independent, unrelated Chinese Han individuals (1457 recipients and 1839 donors) were provided by China Marrow Donor Program (CMDP) for donor-recipient confirmatory typing. SBT, SSOP/HD-SSOP and SSP methods were used to obtain 4-digit alleles. Results: A total of 49, 86, 50, 63 and 24 HLA-A, B, C, DRB1, and DQB1 alleles were observed. Following ASHI CWD criteria, CWD alleles for Chinese Han in our laboratory test and other laboratory reports do not quite correlate with the ASHI CWD alleles: A∗11:53, A∗02:34, A∗02:53N, B∗27:24, B∗46:02, B∗55:12, C∗01:06, C∗03:17, C∗06:06, C∗07:66, C∗07:67, C∗08:22, DRB1∗12:10, DQB1∗03:13 and DQB1∗06:05 are CWD, but are not included in the ASHI CWD list. A series of alleles are Well-Documented alleles and listed in the ASHI CWD list. Conversely, A∗26:03, B∗51:03, C∗12:05, C∗15:09, C∗15:11, C∗17:03, DRB1∗11:07, DRB1∗11:11, DRB1∗13:05, DRB1∗13:13, DRB1∗14:06, DRB1∗14:12, DRB1∗14:22, DRB1∗14:25 and DQB1∗06:11 are rare alleles, but are included in the ASHI CWD list. Conclusions: HLA Ethnic diversity is the main reason for the differences in HLA alleles worldwide. The ASHI HLA CWD alleles help reduce the workload and expenses in high-resolution donor registries and the HLA allele frequencies provide a basis from which to predict the chances of finding HLA matching donors. Our data will be meaningful for the CMDP, for other worldwide donor registries, and for an updated ASHI CWD alleles list. [Copyright &y& Elsevier]

Objective: To investigate the role of different immunoglobulin- like receptor (KIR)haplotypes in haplo- identical hematopoietic stem cell transplantation (HSCT)., Method: Killer cell KIR genotyping was performed on 468 individuals from 156 unrelated families by PCR-SSP. A total of 624 KIR haplotypes from the parents were used for haplotype analysis. Ninety-two patients received haplo-identical HSCT from one of the parents., Results: The family study showed segregation of one A haplotype and at least 20 unique B haplotypes. The frequency of haplotype A was 72.92% (455/624). The most commonly observed haplotypes in group B were B1, B2, and B3, present at a frequency of 10.26%, 5.77%, and 4.48%, respectively. Compared to KIR gene matched donors (n=17), grafts from KIR gene mismatched donors (n= 14) had a positive effect on survival after haplo- identical HSCT for AML/MDS patients (OS: 88.2%vs 42.9%,P=0.015; RFS: 88.2%vs 35.7%,P=0.007). No effect was observed for ALL/NHL patients (OS: 76.0%vs 75.0%,P=0.727; RFS: 68.0%vs 65.0%,P=0.866). A significantly lower survival rate was observed for transplants from AA (n=52) and AB1/AB2 donors (n=15), compared to other group Bx donors (n=25) (OS: 53.3%vs 96.0%,P=0.017; RFS: 53.3%vs 92.0%,P=0.019). Meanwhile, the risk of relapse was much higher in AA group (n=52) compared to Bx group (n=40) (25.0%vs 5.0%,P=0.009). A higher risk of TRM was observed in AB1/AB2 group (P=0.012). In addition, transplant from donors carried Cen-B was associated with an increased survival compared with Cen-A homozygous donors (OS: 94.7%vs 68.5%,P=0.036; RFS: 89.5%vs 64.4%,P=0.045)., Conclusion: Overall, KIR genotyping and haplotype analyses should be useful for selection of the most optimal donors with favorable KIR gene grafts. KIR gene mismatch donors should be preferred for AML/MDS patients. Selecting donors carried Cen- B and avoiding the selection of donors of KIR genotype AA/AB1/AB2 was strongly advisable for haplo-identical HSCT.