Human natural killer (NK) cells are essential for controlling infection, cancer and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B and -C genes, we show that the Chinese Southern Han are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the Chinese Southern Han KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B specific receptors. In all these characteristics, the Chinese Southern Han represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity and effector strength, likely augmenting resistance to endemic viral infections.

Background Blood donor plasma samples were detected by the Ultrio Plus NAT system for HBV, HCV and HIV-1 in Shenzhen blood center, China. Reactive samples underwent further discriminatory testing of a single virus by the same methodology. A large number of cases of non-discriminated reactive (NDR) donors were found, leaving potential risk of transmitting HBV if not deferrals. This study identified those non-discriminated samples. Methods The NDR plasma samples from blood donation screening were detected and classified by additional molecular and serological tests. Molecular characterizations of DNA+ NDR were determined by sequencing analysis. Results A number of 259 (0.21%) NDR plasma samples from screening of 123,280 eligible blood donors were detected, which presented a higher rate (91.1%) of anti-HBc reactivity and nearly half (46.7%) of HBV DNA+ that classified as occult HBV infection (OBI). Most OBI strains were wild-type HBV, but some substitutions V168A, S174 N, V177A, Q129R/L/H, G145A/R in S region of genotype B (OBI B ) and T47K/V/A, P49H/L, Q101R/H/K, S174 N, L175S, V177A, T118 M/R/K, G145R/A/K/E, R160K/N in S region of genotype C (OBI C ) strains were identified in high frequency. Conclusion Nearly half of NDR blood samples were identified as OBI, in which a number of important mutations were detected. NDR donation might have potential risk for HBV transmission, but need to be further investigated.

BACKGROUNDHepatitis B virus (HBV) infection is one of the major concerns for the safety of blood transfusion in high‐prevalent countries such as in China. Prior studies outside of China have shown hepatitis B surface antigen (HBsAg) false‐reactive rate of 0.02% to 0.04%. Similarly, false‐negative HBsAg and HBV DNA results may occur in infected donors. Our study analyzed HBsAg enzyme‐linked immunosorbent assay (ELISA)‐reactive but NAT‐negative donations in Shenzhen Blood Center, China.STUDY DESIGN AND METHODSHBsAg ELISA‐positive/NAT‐negative plasma samples identified from screening 101,025 donations during 2017‐2018 were analyzed by molecular and serologic tests including neutralization, chemiluminescence immunoassays, and various HBV DNA amplification assays. Molecular characterizations of HBsAg‐positive/NAT‐negative samples were determined by quantitative polymerase chain reaction (qPCR) and nested PCR amplification of the basic core and precore promotor regions (295 base pairs) and HBsAg (S) region (496 base pairs).RESULTSScreening of 101,025 eligible blood donations identified 157 (0.16%, 95% confidence interval, 0.13%‐0.18%) HBsAg ELISA‐positive/NAT‐negative plasma samples; of those, 71 (45.2%) were HBsAg confirmed positive by further HBsAg testing and DNA positive by molecular tests with increased sensitivity. Of the 71, all but one was antibody to hepatitis B core antigen reactive without antibody to hepatitis B surface antigen, yielding one recent (window‐period) HBV infection. Of the remaining donations, 80 (51%) were not considered as HBV‐infected donors, and 6 (3.8%) were interpreted as indeterminate since HBsAg results were discordant with unconfirmed HBV DNA results. In the 71 confirmed positives, HBsAg levels ranged from 0.05 to 400 IU/mL and HBV DNA from 6 to 2654 IU/mL; however, the correlation between the two was weak (R2 = 0.24).CONCLUSIONFewer than half of HBsAg ELISA‐positive/NAT‐negative samples were confirmed as HBsAg positive. Our study demonstrates that in highly HBV‐endemic countries, assays with high sensitivity and specificity may be required.

Interactions of human natural killer (NK) cell inhibitory receptors with polymorphic HLA-A, -B and -C molecules educate NK cells for immune surveillance against tumor cells. The KIR A haplotype encodes a distinctive set of HLA-specific NK cell inhibiting receptors having strong influence on immunity. We observed higher frequency of KIR A homozygosity among 745 healthy Chinese Southern Han than 836 adult patients representing three types of leukemia: ALL (OR = 0.68, 95% CI = 0.52–0.89, p = 0.004), AML (OR = 0.76, 95% CI = 0.59–0.98, p = 0.034), and CML (OR = 0.72 95% CI = 0.51–1.0, ns). We observed the same trend for NHL (OR = 0.47 95% CI = 0.26–0.88 p = 0.017). For ALL, the protective effect of the KIR AA genotype was greater in the presence of KIR ligands C1 (Pc = 0.01) and Bw4 (Pc = 0.001), which are tightly linked in East Asians. By contrast, the C2 ligand strengthened protection from CML (Pc = 0.004). NK cells isolated from KIR AA individuals were significantly more cytotoxic toward leukemic cells than those from other KIR genotypes ( p < 0.0001). These data suggest KIR allotypes encoded by East Asian KIR A haplotypes are strongly inhibitory, arming NK cells to respond to leukemogenic cells having altered HLA expression. Thus, the study of populations with distinct KIR and HLA distributions enlightens understanding of immune mechanisms that significantly impact leukemia pathogenesis.

SUMMARYLow testosterone is associated with late-onset hypogonadism (LOH) and obesity. Recently, studies have shown that four single nucleotide polymorphisms (SNPs), rs12150660, rs727428, rs5934505, and rs10822184, are associated with testosterone levels in populations of European descent. Therefore, we investigated whether the SNP loci are related to low testosterone, LOH, or obesity in a Chinese Han population. Ruling out co-morbidities, DNA was prepared from 409 men (aged 40-65 years) with low serum testosterone (defined as total testosterone <11.6 nmol/L) and 1 : 1 normal controls (matched age, body mass index (BMI), and the same living area) who were selected from 6898 males. According to the same standards, 310 men with LOH and 1 : 1 normal controls were selected from 6898 males. Excluding the cases with an unreliable sequencing result, genetic analyses were performed. The minor allele frequencies of the SNP loci rs12150660, rs727428, rs5934505, and rs10822184 were 0.1%, 44.6%, 18.7%, and 38.9%, respectively. rs5934505 was associated with the serum total testosterone and calculated free testosterone (CFT) levels (p = 0.045 and p = 0.021). rs5934505 (C>T) was associated with an increased risk of low total testosterone, low CFT, and LOH and adjusted for other factors, with an odds ratio (OR) of 2.01 (1.34-3.01), 2.14 (1.42-3.20), and 1.64 (1.04-2.58). rs10822184 was significantly correlated with weight and BMI (p = 0.035 and p = 0.027). rs10822184 (T>C) was associated with an increased risk of overweight and obesity. We adjusted for other factors, with odds ratios (ORs) of 1.94 (1.36-2.78) and 1.56 (1.00-2.43). In summary, our study provided convincing evidence that rs5934505 (C>T) was associated with the risk of low testosterone and LOH in Chinese populations. We were the first to find that rs10822184 (T>C) was significantly correlated with the risk of overweight and obesity in Chinese populations. However, further large and functional studies are warranted to confirm our findings.