Visually induced γ band rhythm in spatial summation beyond the receptive field in mouse primary visual cortex.

Recent studies in many kinds of mammals have established the existence of multiple γ rhythms in the cerebral cortex subserving different functions. In the primary visual cortex (V1), visually induced γ rhythms are dependent on stimulus features. However, experimental findings of γ power induced by varying the size of the drifting grating are inconsistent. Here, we reinvestigated the spatial summation properties of visually induced spike and γ rhythm activities in mouse V1. Our results show that drifting sinusoidal grating stimuli mainly induce 2 γ band rhythms, including a low-frequency band (25-45 Hz) and a high-frequency band (55-75 Hz). Unlike previous findings, we discovered that visually induced γ power could also exhibit extrareceptive field (ERF) modulatory properties. The modulation by ERF stimulation could be either suppressive, countersuppressive, or nonsuppressive, mostly similar to the local spike activity. Moreover, further analysis of the neuron group exhibiting surround suppression in both spike and γ activity revealed that the strength of the surround suppression and the receptive field size showed moderate correlations between measurements by spike and γ rhythm activity. Our findings improve the understanding of the characteristics and neural mechanisms of induced γ rhythms in visual spatial summation.

Deep learning-mediated prediction of concealed accessory pathway based on sinus rhythmic electrocardiograms.

BACKGROUND: Concealed accessory pathway (AP) may cause atrial ventricular reentrant tachycardia impacting the health of patients. However, it is asymptomatic and undetectable during sinus rhythm. METHODS: To detect concealed AP with electrocardiography (ECG) images, we collected normal sinus rhythmic ECG images of concealed AP patients and healthy subjects. All ECG images were randomly allocated to the training and testing datasets, and were used to train and test six popular convolutional neural networks from ImageNet pre-training and random initialization, respectively. RESULTS: We screened 152 ECG recordings in concealed AP group and 600 ECG recordings in control group. There were no statistically significant differences in ECG characteristics between control group and concealed AP group in terms of PR interval and QRS interval. However, the QT interval and QTc were slightly higher in control group than in concealed AP group. In the testing set, ResNet26, SE-ResNet50, MobileNetV3_large_100, and DenseNet169 achieved a sensitivity rate more than 87.0% with a specificity rate above 98.0%. And models trained from random initialization showed similar performance and convergence with models trained from ImageNet pre-training. CONCLUSION: Our study suggests that deep learning could be an effective way to predict concealed AP with normal sinus rhythmic ECG images. And our results might encourage people to rethink the possibility of training from random initialization on ECG image tasks.

Dynamic mRNA expression of donor-derived activating KIR genes and their significant effects on clinical outcome after haematopoietic stem cell transplantation.

Numerous reports suggest that activating killer immunoglobulin-like receptors (aKIRs) of natural killer (NK) cells, in addition to inhibitory KIRs (iKIRs), play a prognostic role after allogeneic haematopoietic stem cell transplantation (allo-HSCT). We aimed to investigate the association between the dynamic expression of KIRs on NK cells and the outcomes, particularly regarding graft-versus-host disease (GvHD). This study retrospectively enrolled 260 pairs of donors and recipients who had undergone allo-HSCT without in-vitro T cell depletion. The mRNA transcription level of KIRs was determined by quantitative real-time polymerase chain reaction (RT-qPCR). The levels of aKIR transcripts were decreased more than those of iKIRs during the occurrence of GvHD. The transcription levels of KIR2DS2 and KIR2DS4 in the patients developing GvHD, compared with those who were at a tolerance state, showed the most significant decrease in the month at their peak transcription levels (p = 0.03, p = 0.002). Significantly decreased expression of KIR2DS1 (p = 0.02), KIR2DS3 (p = 0.04) and KIR2DS5 (p = 0.04) in the GvHD group was observed when the transcription level reached a maximum. High expression of KIR3DS1 was associated with superior overall survival (OS) (p < 0.001). The expression of KIR2DS4 in the KIR genotype Bx group decreased more during GvHD, particularly at 3M (p = 0.02). These findings suggest that KIR genes are potential post-HSCT biomarkers and dynamic changes in the KIR transcription levels can be detected to better predict the occurrence and evaluate the treatment of GvHD after transplantation.

Study of KIR gene expression at the mRNA level in specific donor-derived NK cells after allogeneic HSCT.

The function of natural killer (NK) cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is regulated by the balance between inhibitory KIRs (iKIRs) and activating KIRs (aKIRs). However, few studies have examined the subsequent expression of KIR genes unique to the donor. We defined the set of KIR genes expressed only in the donor and designed a method for measuring the expression of these KIR genes by quantitative real-time polymerase chain reaction (RT-qPCR) based on genetic cloning techniques. In this study, we evaluated the recovery pattern of KIR genes in 252 donor-recipient pairs. The expression of each KIR unique to the donor was in line with that of KIR genes shared by the donor and recipient, such as KIR2DS1, KIR3DS1, KIR2DS4, or KIR2DS3. The timing of the peak mRNA expression of aKIRs unique to the donor was inconsistent but occurred within the first 3 months posttransplantation, whereas the peak mRNA expression of iKIRs was consistently observed in the third month after transplantation. The expression of KIR2DL2 in the third month posttransplantation was significantly higher in the transplant recipients than in the donors (p = 0.01). The KIR2DL1 and KIR3DL1 levels in the transplant recipients in the second and third months posttransplantation were also obviously higher than the donor levels (p < 0.0001). Thus, these observations should be considered when attempting to predict the correlation between mRNA expression and prognosis after allo-HSCT.

Synthetic imaging through wavy water surface with centroid evolution.

Imaging through a wavy water surface is a challenging task, as the wavy water surface introduces anisoplanatism effects difficult to model and track. A typical recovery method is usually involving multiple-stage processing on a pre-acquired image sequence. A new progressive restoration scheme is demonstrated, it can run simultaneously with image acquisition and mitigate both distortion and blur progressively. This method extends the anisotropic evolution in lucky region fusion with a novel progressive optical flow based de-warping scheme, centroid evolution. A comparison has been made with other state-of-art techniques, the proposed method can create comparable results, even with much less frames acquired. Experiments with real through-water scenes have also proved the effectiveness of the method.

Donor Killer Immunoglobulin-Like Receptor Profile Bx1 Imparts a Negative Effect and Centromeric B-Specific Gene Motifs Render a Positive Effect on Standard-Risk Acute Myeloid Leukemia/Myelodysplastic Syndrome Patient Survival after Unrelated Donor Hematopoietic Stem Cell Transplantation.

Donor killer immunoglobulin-like receptor (KIR) group B profiles (Bx) and homozygous of centromeric motif B (Cen-B/B) are the most preferable KIR gene content motifs for hematopoietic stem cell transplantation (HSCT). The risk of transplant from Bx1 donors and the benefit of the presence of Cen-B (regardless of number) were observed for standard-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients in this 4-year retrospective study. A total of 210 Chinese patients who underwent unrelated donor HSCT were investigated. Donor KIR profile Bx was associated with significantly improved overall survival (OS; P = .026) and relapse-free survival (RFS; P = .021) and reduced nonrelapse mortality (NRM; P = .017) in AML/MDS patients. A significantly lower survival rate was observed for transplants from Bx1 donors compared with Bx2, Bx3, and Bx4 donors for patients in first complete remission (n = 82; OS: P = .024; RFS: P = .021). Transplant from donors with Cen-B resulted in improved OS (HR = .256; 95% CI, .084 to .774; P = .016) and RFS (HR = .252; 95% CI, .084 to .758; P = .014) in AML/MDS patients at standard risk. However, this particular effect did not increase with a higher number of Cen-B motifs (cB/B versus cA/B; OS: P = .755; RFS: P = .768). No effect was observed on high-risk AML/MDS, acute lymphoblastic leukemia/non-Hodgkin lymphoma, and chronic myelogenous leukemia patients. Avoiding the selection of HSCT donors of KIR profile Bx1 is strongly advisable for standard-risk AML/MDS patients. The presence of the Cen-B motif rather than its number was more important in donor selection for the Chinese population.

KIR2DS4 and Its Variant KIR1D Are Associated with Acute Graft-versus-Host Disease, Cytomegalovirus, and Overall Survival after Sibling-Related HLA-Matched Transplantation in Patients with Donors with KIR Gene Haplotype A.

Outcomes for hematopoietic stem cell transplantation (HSCT) in various donor and recipient killer immunoglobulin-like receptor (KIR) genotypes have been studied extensively. The associations between KIR2DS4 and its variant KIR1D with outcomes of HSCT from a sibling-related HLA-matched donor with KIR haplotype A have not been explored, however. To study this, we genotyped donor-recipient pairs and divided 165 recipients of HSCT from a KIR gene haplotype A donor into 3 groups: 2DS4+/2DS4+ (2 intact KIR2DS4 alleles), 2DS4+/1D+ (heterozygous), and 1D+/1D+ (homozygous for the deletion variant KIR1D). No difference in the recovery of neutrophils and platelets among the 3 groups was observed. The cumulative incidence of grade III-IV acute graft-versus-host disease (aGVHD) within day +100 was 28.94% in the 2DS4+/2DS4+ group, 14.11% in the 2DS4+/1D+ group, and 44.44% in the 1D+/1D+ group (P = .0159). Multivariate analysis identified 1D+/1D+ as an independent risk factor for aGVHD (hazard ratio [HR], 4.221; 95% confidence interval [CI], 1.470 to 12.124; P = .007). In contrast, the cumulative incidences of chronic GVHD, 3-year cumulative relapse, and treatment-related mortality did not differ significantly among the 3 groups. The rate of cytomegalovirus (CMV) reactivation was 46.96% in the 2DS4+/2DS4+ group, 20.16% in the 2DS4+/1D+ group, and 53.25% in the 1D+/1D+ group (P = .0017). Multivariate analysis identified 2DS4+/1D+ as an independent protective factor for CMV reactivation (HR, 0.268; 95% CI, 0.125 to 0.574; P = .001). Although overall survival (OS) did not differ among the groups in the first year, the 2DS4(+)/2DS4(+) group had significantly better OS than the other groups after 1 year (P = .0361). In patients with advanced-stage disease, the 3-year probability of disease-free survival was 51.06% in the 2DS4+/2DS4+ group, 34.01% in the 2DS4+/1D+ group, and 0% in the 1D+/1D+ group (P = .0314). Collectively, our data suggest that the KIR 2DS4/1D allelic variance is associated with the outcome of sibling-related HLA-matched HSCT, and that donor subclassification of KIR 2DS4/1D alleles should be considered in this setting.

Donor selection for killer immunoglobulin-like receptors B haplotype of the centromeric motifs can improve the outcome after HLA-identical sibling hematopoietic stem cell transplantation.

After hematopoietic stem cell transplantation (HSCT), natural killer (NK) cell alloreactivity in HLA cells of recipients is regulated by killer immunoglobulin-like receptors (KIRs) on donor NK cells. The effect of KIRs on HSCT outcomes is controversial, particularly in those undergoing HLA-identical sibling HSCT. In this study, effects of KIR and HLA genotypes on the HSCT outcome were investigated in a 5-year retrospective study comprising 219 patient-donor pairs undergoing HLA-identical sibling HSCT for myeloid and lymphoid malignancies. We found that 39.7% (87 of 219) of these pairs, which were KIR mismatched, had better overall survival (OS) and reduced grade III to IV acute graft-versus-host disease (aGVHD), especially in acute myeloid leukemia (AML) patients. Bx1 donor KIR genotype with haplotype B on a telomeric region was a risk factor for the OS and relapse-free survival (RFS). Donor centromeric (c) and telomeric (t) KIR haplotype analysis showed that donor KIR cB-tA/tB was associated with improved OS and RFS compared with cA-tA or cA-tB. Furthermore, donor KIR B haplotype of the centromeric motifs (Cen-B) was an independent beneficial factor in improving OS and RFS and in protecting from relapse after HSCT. In AML patients, the occurrence of aGVHD was significantly lower in HLA-C1 group compared with that in HLA-C2 group, although such effect was not observed in patients with acute lymphoblastic leukemia or chronic myelogenous leukemia. Our results suggest that KIR could impact outcome and donor KIR haplotype with Cen-B confer significant survival benefits to HLA-identical sibling HSCT.

HLA-DPB1 and DPA1 ~ DPB1 linkage mismatch affects the survival of recipients receiving HLA-14/14 matched unrelated donor HSCT.

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.

Donor selection for KIR B haplotype of the centromeric motifs can improve the outcome after HLA-identical sibling hematopoietic stem cell transplantation.

After hematopoietic stem cell transplantation (HSCT), natural killer (NK) cell alloreactivity in human leukocyte antigen (HLA) cell of recipients is regulated by killer immunoglobulin-like receptors (KIRs) on donor NK cells. The effect of KIRs on HSCT outcomes is controversial, particularly in those undergoing HLA-identical sibling HSCT. In this study, effects of KIR and HLA genotypes on the HSCT outcome were investigated in a 5-year retrospective study comprising 219 patient-donor pairs undergoing HLA-identical sibling HSCT for myeloid and lymphoid malignancies. We found that 39.7% (87/219) of these pairs who were KIR mismatched had better overall survival (OS) and reduced III-IV acute graft-versus-host disease (aGVHD), especially in acute myeloid leukemia (AML) patients. Bx1 donor KIR genotype with haplotype B on a telomeric region was a risk factor for the OS and relapse-free survival (RFS). Donor centromeric (c) and telomeric (t) KIR haplotype analysis showed that donor KIR cB-tA/tB was associated with improved OS and RFS compared with cA-tA or cA-tB. Furthermore, donor KIR B haplotype of the centromeric motifs (Cen-B) was an independent beneficial factor in improving OS and RFS and in protecting from relapse after HSCT. In AML patients, the occurrence of aGVHD was significantly lower in HLA-C1 group compared to that in HLA-C2 group, while such effect was not observed in patients with acute lymphoblastic leukemia or chronic myelogenous leukemia. Our results suggest that KIR could impact outcome and donor KIR haplotype with Cen-B confer significant survival benefits to HLA-identical sibling HSCT.

Immune function assay (ImmuKnow) as a predictor of allograft rejection and infection in kidney transplantation.

BACKGROUND: 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 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 fell 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 with 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 with 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 with 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.

[The association of killer cell immunoglobulin like receptor gene polymorphism with cytomegalovirus infection after hematopoietic stem cell transplantation].

OBJECTIVE: To explore the influence of the killer cell immunoglobulin like receptor (KIR) gene polymorphism on cytomegalovirus (CMV) infection and pathogenesis after hematopoietic stem cell transplantation (HSCT). METHODS: The KIR genotype was determined by sequence-specific primer polymerase chain reaction (PCR-SSP) in 138 pairs of donors and recipients before HSCT during October, 2005 and May, 2011. Posttransplant monitoring for CMVpp65 antigen was performed by indirect immune histochemically assays since week 2 after transplantation. The differences between CMV positive group and negative group, inhibitive and active KIR of donors and recipients, and KIR haplotype frequency of donors and recipients were analyzed. RESULTS: There were no significant differences in frequency of KIR gene and haplotype AA, AB, BB between the donors and recipients. The frequencies of 2DS2 and 2DS4 * 003-007 of donors in CMV positive group were obviously lower than those in CMV negative group with significant differences (8% vs 16% , P = 0.0420; 3% vs 13%, P = 0.0050). There was no significant difference in KIR gene between CMV positive group and CMV negative group. The CMV infection rates of haplotype AA, BB, AB donors were 64.38%, 36.84% and 50.00%, while CMV infection rates of haplotype AA, BB, AB recipients were 53.73%, 46.15% and 51.72%, respectively. The CMV infection rate was higher in the patients received KIR haplotype AA donor than in those received KIR haplotype BB donor (36.84% vs 64.38%, P = 0.0299). 2DS4 x 003-007 and haplotype BB of donor were found associated with CMV infection in multifactor analysis. CONCLUSION: KIR genotypes of donors are associated with CMV infection after HSCT.

Use of next-generation sequencing to detect polymorphism of 11 HLA allele loci in the Chinese Han population and variance from other common and well-documented lists.

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.

Establishment of NGS-based HLA 9-locus haplotypes in the Eastern Han Chinese population highlights the role of HLA-DP in donor selection for transplantation.

We collected HLA typing data from 653 families in the Eastern Han Chinese population. HLA-A, B, C, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1 (HLA-11 loci) typing of 1781 subjects was performed using a commercial next-generation sequencing (NGS) method in our laboratory. The phasing of haplotypes in each family was determined by Mendelian segregation. Haplotype analysis revealed 1634 different haplotypes among a total of 2230 haplotypes. The predominant haplotype was A*30:01-C*06:02-B*13:02-DRB1*07:01-DRB4*01:03-DQA1*02:01-DQB1*02:02-DPA1*02:01-DPB1*17:01 (HF = 4.04%), followed by A*02:07-C*01:02-B*46:01-DRB1*09:01-DRB4*01:03-DQA1*03:02-DQB1*03:03-DPA1*02:02-DPB1*05:01 (HF = 1.84%) and A*33:03-C*03:02-B*58:01-DRB1*03:01-DRB3*02:02-DQA1*05:01-DQB1*02:01-DPA1*01:03-DPB1*04:01 (HF = 1.48%), accounting for 7.35% of the total. Meanwhile 76.41% of all haplotypes were observed only once or twice (HF < 0.1%). Different from HLA-DRB3/4/5 and DQA1 loci, DP linkage markedly increased haplotype variation by 34.82% based on the 5-locus haplotype. The much weaker linkage disequilibrium (LD) of DQB1-DPB1 indicated the reason. We observed 10 analyzable recombination events, most of which occurred at DP loci. Even with the same common 5-locus haplotype, HLA-DP linkage alters the haplotype diversity and frequency. Analysis of related haplotype assignment and unrelated recipient-donor pairs matching at the 9-locus haplotype revealed that HLA-DP affects the donor selection strategy. Haplotype study of a large sample size using NGS identified linkage haplotypes beyond the 5 loci. LD, recombination events, and haplotype variation caused by DP loci emphasized that HLA 9-locus haplotype matching should be considered in donor selection, particularly the effect of DP loci. The finding lays the foundation for further studies on the effect of HLA-DP mismatch on transplantation.

Posttransplant de novo DSA and NDSA affect GvHD, OS, and DFS after haplo-HSCT in patients without pre-existing HLA antibodies of hematological malignancies.

To examine the production time, type, and MFI of post-transplantation de novo HLA antibodies, and their effects on haplo-HSCT outcomes, we retrospectively included 116 patients who were negative for pre-existing HLA antibodies. In total, 322 serum samples from pre-transplantation to post-transplantation were dynamically tested by Luminex and single-antigen bead reagents. Patients were divided into: HLA antibody persistently negative group (group 1), the de novo HLA antibody transiently positive group (group 2), the de novo HLA antibody non-persistently positive group (group 3), and the de novo HLA antibody persistently positive group (group 4). Group 4 included DSA+non-DSA (NDSA) (group 4a) and NDSA (group 4b) groups. The detection rate of de novo HLA antibodies was 75.9% (88/116). The median MFI for de novo HLA antibodies was 2439 (1033-20162). The incidence of II-IV aGvHD was higher in group 2 than in group 1 (52.6% vs 17.9%, P < 0.01); in group 4a than in group 1 (87.5% vs 17.9%, P < 0.001); and in group 4a than in group 4b (87.5% vs 40.0%, P = 0.001). The DFS (37.5% vs 85.7%, P < 0.01) and OS (37.5% vs 85.7%, P < 0.01) of group 4a were lower than those of group 1. The DFS (48.0% vs 85.7%, P < 0.01) and OS (56.0% vs 85.7%, P = 0.03) of group 4b were lower than those of group 1. Multivariate analysis showed that de novo HLA antibody being transiently positive (HR: 5.30; 95% CI: 1.71-16.42, P = 0.01) and persistently positive (HR: 5.67; 95% CI: 2.00-16.08, P < 0.01) were both associated with a higher incidence of II-IV aGvHD. Persistently positive de novo HLA antibodies were a risk factor for reduced DFS (HR: 6.57; 95% CI: 2.08-20.70, P < 0.01) and OS (HR: 5.51; 95% CI: 1.73-17.53, P < 0.01). DSA and NDSA can be detected since 15 days after haplo-HSCT in patients without pre-existing HLA antibodies, and affect aGvHD, DFS, and OS. Haplo-HSCT patients must be monitored for HLA antibodies changes for appropriate preventive clinical management, and we recommend that 1-month post-transplantation is the best test time point.

[A study on allele frequencies and mismatching proportion of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution donor-recipient typing in Chinese Han population].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Population-specific criterion to distinguish killer cell immunoglobulin-like receptor genotypes and haplotypes in a large Eastern Han population.

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.

[The role of different KIR haplotypes in haplo-identical hematopoietic stem cell transplantation].

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.