[Analysis of the reentry status of blood donors with reactive bloodborne pathogen screening markers in Hangzhou City].

Objective: To explore the reentry rate of reactive blood donors in the bloodborne pathogen infection screening in Hangzhou City, and analyze the donation behavior of those who successfully returned. Methods: A retrospective analysis of the return data of blood donors with reactive bloodborne pathogen screening markers was conducted at Zhejiang Provincial Blood Center from June 2017 to May 2022. The reentry process for blood donors with reactive bloodborne pathogen screening markers in Hangzhou City is as follows: after the initial screening period of 6 months, donors can voluntarily apply for return to the blood center. Samples are collected and subjected to routine enzyme-linked immunosorbent assay (ELISA) screening for HBsAg, anti-HCV, HIV Ab/Ag, and anti-TP, as well as a single nucleic acid (HIV/HCV/HBV) test. For samples that show non-reactivity in both ELISA and nucleic acid tests, serum biomarker testing for the reasons of exclusion is performed using chemiluminescence immunoassay (CLIA), and those with non-reactivity are allowed to return. Results: A total of 4 583 reactive blood donors who met the criteria for re-entry applied for reentry, out of which 475 applications were received from donors in the Hangzhou area. Among these, 279 donors were successfully readmitted, resulting in a success rate of 58.74% (279/475). By the end of December 2021, out of the 174 donors who successfully returned, 114 donors chose to donate again. They collectively donated 39 530 ml of whole blood and 1 147.2 therapeutic doses of platelets. Among these, 21 donors once again showed reactivity for pathogen infection biomarkers, accounting for 18.42% (21/114). Conclusion: The reentry strategy has somewhat mitigated the attrition of blood donors. Nevertheless, there are instances where donors who were successfully readmitted show reactivity once more in the screening for pathogen infection biomarkers.

Characterization of a novel allelic variant in HLA-B*40 lineage, HLA-B*40:298:02, by cloning and sequencing.

A novel allelic variant in HLA-B*40 lineage, HLA-B*40:298:02, has been identified in an individual of Han ethnicity afflicted with nasopharyngeal carcinoma in Hunan province, southern China. Following polymerase chain reaction-Sanger sequence-based typing (PCR-SBT), this new variant was further confirmed by two distinct strategies of cloning and sequencing. HLA-B*40:298:02 differs from HLA-B*40:298:01 by a single synonymous cytosine substitution at nucleotide position 26 (T→C) in exon 3, which corresponds to codon 99 of the mature HLA-B mRNA molecule. This new allele has an estimated frequency of 0.0002, in about 2,500 sequence-based typed subjects from the same population.

Characterization of a novel HLA-B*39:01:01-related allele, HLA-B*39:130, by cloning and phasing.

A novel HLA-B*39:01:01-related variant, HLA-B*39:130, has been identified in a normal individual of Han ethnicity in Hunan province, southern China. Following Sanger polymerase chain reaction-sequence-based typing (PCR-SBT), this new allele was further confirmed by cloning, phasing and sequencing. Aligned with HLA-B*39:01:01, HLA-B*39:130 has a nonsynonymous thymine substitution at nucleotide position 94 in exon 4, resulting in amino acid change from threonine to isoleucine at codon 214 (ACA→ATA) of the mature HLA-BmRNA molecule.

A new MICA allele, MICA*007:07, characterized by cloning and sequencing.

A new MICA allelic variant, MICA*007:07, was identified in an individual of Mongol ethnicity in the Inner Mongolia Autonomous Region, northern China. Following polymerase chain reaction-sequence-based typing (PCR-SBT), this new allele was further confirmed by cloning and sequencing. MICA*007:07 differs from MICA*007:01 by a synonymous mutation from G to A at the 2nd nucleotide position in exon 2. MICA*007:07 was linked to HLA-B*27:05.

MICA, MICB Polymorphisms and Linkage Disequilibrium with HLA-B in a Chinese Mongolian Population.

In this study, polymorphisms of major histocompatibility complex class I chain-related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)-B gene were investigated for 158 unrelated Chinese Mongolian subjects recruited from central Inner Mongolia Autonomous Region, northern China, by polymerase chain reaction-sequence-based typing (PCR-SBT) and cloning. Collectively, 79 alleles, including 20 MICA, 12 MICB and 47 HLA-B alleles, were identified. MICA*008:01 (21.2%), MICB*005:02 (48.1%) and HLA-B*51:01 (7.91%) were the most common alleles. Significant global linkage disequilibrium (LD) was detected between HLA-B and MICA, HLA-B and MICB, and MICA and MICB loci (all P < 0.000001). The most frequent haplotypes were HLA-B*51:01-MICA*009:01 (7.28%), HLA-B*58:01-MICB*008 (6.96%), MICA*010-MICB*005:02 (13.92%) and HLA-B*58:01-MICA*002:01-MICB*008 (6.96%). HLA-B-MICA haplotypes such as HLA-B*50:01-MICA*009:02 were associated with single MICB allele. Some HLA-B-MICA haplotypes were associated with multiple MICB alleles, including HLA-B*51:01-MICA*009:01. One novel MICB allele, MICB*031, was identified, which has possibly arisen from MICB*002:01 through single mutation event. We also confirmed the existence of a recently recognized MICA allele, MICA*073, whose ethnic origin has not been previously described. Genotype distributions at MICA, MICB and HLA-B were consistent with a neutrality model. Our results provide new insight into MIC genetic polymorphisms in Chinese ethnic groups. Findings shown here are important from an anthropologic perspective and will inform future studies of the potential role of MIC genes in allogeneic organ transplantation and HLA-linked disease association in populations of related ancestry.

Characterization of a new HLA-A allele, HLA-A*02:07:08, by cloning and sequencing.

In this report, we present a novel HLA-A*02:07 allele, HLA-A*02:07:08. HLA-A*02:07:08 was identified in an individual of Han ethnicity in Hunan province, southern China. Following polymerase chain reaction-sequence-based typing (PCR-SBT), this new allele was further confirmed by cloning and sequencing. HLA-A*02:07:08 differs from HLA-A*02:07:01 by a single synonymous C to T substitution at nucleotide position 131 in exon 3.

Characterization of a novel HLA-B*40 allele, HLA-B*40:186:02, by cloning and sequencing.

A novel HLA-B*40 variant, HLA-B*40:186:02, has been identified by cloning and sequencing in a southern Chinese Han population. Aligned with HLA-B*40:01:01, HLA-B*40:186:02 has a nonsynonymous cytosine mutation at nucleotide position 165 in exon 2, leading to amino acid change from glycine to arginine at codon 56. It differs from HLA-B*40:186:01 by a synonymous change (adenine to cytosine) at position 165 in exon 2.

Characterization of a novel MICA allele, MICA*012:05, by cloning and sequencing.

A new MICA allelic variant, MICA*012:05, has been identified in a Chinese Mongolian population. Following polymerase chain reaction-sequence-based typing (PCR-SBT), this new allele was further confirmed by cloning and sequencing. MICA*012:05 was linked to an HLA-A*24-C*01-B*55:02-DRB1*09 haplotype. MICA*012:05 differs from MICA*012:01 by a single synonymous C to T substitution at nucleotide position 269 in exon 3.

A novel HLA allele, HLA-DQB1*02:57, was identified by polymerase chain reaction sequence-based typing in a Chinese individual.

HLA-DQB1*02:57 has one base substitution at position 260 T>C in exon 2 from HLA-DQB1*02:01:01.

HLA-C*06:103, a novel allele was identified in a Chinese patient awaiting hematopoietic stem cell transplantation.

HLA-C*06:103 shows four nucleotides difference from that of HLA-C*06:02:01:01.

Two novel alleles, HLA-B*46:01:11 and HLA-B*51:01:39 were identified in Chinese bone marrow donors.

HLA-B*46:01:11 has 219 G>A compared with HLA-B*46:01:01, and HLA-B*51:01:39 shows 561 G>A with HLA-B*51:01:01.

Two novel HLA-DQB1*03:03 alleles, HLA-DQB1*03:03:08 and DQB1*03:03:13, were identified in Chinese individuals.

Compared with HLA-DQB1*03:03:02:01, HLA-DQB1*03:03:08 and DQB1*03:03:13 have 330 G>C and 349 T>C changes, respectively.

A novel allele, HLA-DRB1*10:07 was identified in a Chinese individual.

HLA-DRB1*10:07 shows one nucleotide different from HLA-DRB1*10:01:01 at position 328 in exon 2.

Identification a novel HLA-B*27:105 allele in a Chinese bone marrow donor by polymerase chain reaction sequence-based typing.

HLA-B*27:105 has one nucleotide change from HLA-B*27:04:01 at nucleotide position 404 from G to A.

Identification of a novel HLA-A*02:06:14 allele by polymerase chain reaction sequence-based typing in a Chinese bone marrow donor.

HLA*02:06:14 differs from HLA-A*02:06:01 by a single nucleotide substitution G > A at position 246.

A novel HLA-A*32 allele, A*32:67 was identified by polymerase chain reaction sequence-based typing in a Chinese individual.

HLA-A*32:67 has a single nucleotide difference at position 286 C>A compared with HLA-A*32:01:01.

Two novel alleles, HLA-A*02:07:06 and HLA-A*02:426, were identified in Chinese individuals.

HLA-A*02:07:06 shows 285 A>C and HLA-A*02:426 has 763 G>A change compared with HLA-A*02:07:01.

Sequence-based typing of HLA-A gene in 930 patients with nasopharyngeal carcinoma in Hunan province, southern China.

In this study, we typed 930 cases of nasopharyngeal carcinoma (NPC) and 1134 normal controls recruited from Hunan province, southern China for human leukocyte antigen-A (HLA-A) locus by sequencing exons 2-4. Very significant associations between HLA-A*02:07, HLA-A*11:01 and NPC were established [25.7% vs 16.18%; odds ratio, OR (95% confidence interval, CI) = 1.79 (1.54-2.09), P < 0.0001 and 21.1% vs 30.42%, OR (95% CI) = 0.61 (0.53-0.70), P<0.0001, respectively]. Further analysis of the molecular basis underlying these associations suggests that cysteine (C) at codon 99 of α2-helix of HLA-A protein is probably deleterious and confers risk to NPC. Convincing evidence was uncovered for negative association of a rare allele in southern Chinese populations, HLA-A*31:01, with NPC [0.22% vs 2.12%, OR (95% CI) = 0.1 (0.04-0.28), P < 0.0001]. rs1059449-A, which encodes arginine (R) at codon 56 of α1-helix of HLA-A protein, was postulated to be crucial for such a pattern of negative association with NPC. A subset of NPC cases (N = 632) and normal controls (N=712) were tested for anti-virus capsid antigen (anti-VCA) immunoglobulin A (IgA), very significant difference in seropositivity for anti-VCA IgA was observed between the two groups [67.56% vs 6.46%, OR (95% CI) = 30.16 (21.42-42.46), P < 0.0001]. However, seropositivity for anti-VCA IgA did not correlate with HLA-A allelic typing in both groups.

KIR3DL1 genetic diversity and phenotypic variation in the Chinese Han population.

Allelic polymorphism and expression variation of killer cell immunoglobulin-like receptor (KIR) 3DL1 on natural killer (NK) cells differ among populations. To determine whether the phenotypic variants are due to KIR polymorphism, transcription or copy number, the allelic polymorphism, mRNA levels and antigen expression of KIR3DL1 were assessed in 162 individuals. We characterized 13 KIR3DL1 alleles, five of which were novel. In addition, 21 genotypes were identified. The correlation between the binding patterns of NK cells to anti-KIR3DL1 and KIR3DL1 alleles was also examined. NK cells with different 3DL1 alleles showed distinct binding levels to anti-KIR3DL1. The binding frequencies of NK cells to anti-KIR3DL1 were not accordant with their binding levels, but both associated with the allele copy numbers. The mRNA expression amounts of individuals with two copy alleles were higher than those of individuals with one copy allele. Our data indicate that both the allele copy number and polymorphism of KIR3DL1 influence the antigen expression on the NK-cell surface, but only the copy number was associated with mRNA expression.

Genomic full-length sequence of a novel HLA-B*39:01:01:03 allele was identified in a Chinese individual.

HLA-B*39:01:01:03 allele differs from HLA-B*39:01:01:01 allele by a single nucleotide substitution.