Search

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]

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]

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]

Antiepileptic drugs frequently cause cutaneous adverse reactions (cADRs). Numerous studies have reported associations between human leukocyte antigen (HLA) alleles and cADRs caused by single antiepileptic drug in Southern Han Chinese people. However, the relationship between the HLA allele and cADRs sequentially induced by two or more antiepileptic drugs (AEDs-induced cross-reactivity) is unclear. To explore the associations between HLA alleles and AEDs-induced cross-reactivity, we prospectively recruited patients with AEDs-induced cross-reactivity from 2009 to 2017 and performed high-resolution genotyping to detect the HLA-A, B, C, and DRB1 alleles in patients for comparison with normal controls. To verify the important genotype, we compared its presence in patients with cross-reactivity to enlarged normal controls, and its presence in patients with carbamazepine (CBZ)-induced maculopapular exanthema (MPE) to CBZ-tolerant controls. Further, the important allele was replicated by meta-analysis. Twenty-three patients with AED-induced cross-reactivity and 500 healthy individuals were enrolled from Southern China. All patients had a mild rash without mucosal or systemic involvement. The HLA-B*13:01 allele was present in 34.78% (8/23) of patients, 14.60% (73/500) of healthy individuals, and 14.5% (763/5,270) healthy individuals, revealing a significant association (8/23 vs. 73/500; P = 0.02; OR: 3.12; 95% CI: 1.28–7.62; 8/23 vs. 763/5,270; P = 0.014; OR: 3.15; 95% CI: 1.33–7.46). HLA-B*13:01 was presented numerically higher in CBZ-induced MPE than that in CBZ-tolerant individuals without statistical significance (33/145, 22.76%, vs. 28/179, 15.64%; P = 0.103). Meta-analysis revealed an association between HLA-B*13:01 and cADRs induced by single AEDs or/and non-AEDs in Chinese and Thai populations (P = 0.000). This study suggests that HLA-B*13:01 is potentially associated with AED-cADRs in general, possibly with stronger effect in cross-reactivity. Screening for HLA-B*13:01 prior to starting AEDs therapy may help to avoid cADRs. However, this association requires further analysis in a multi-center study with a larger sample size. [ABSTRACT FROM AUTHOR]

HLA-C*06:02:102 differs from HLA-C*06:02:01:01 by one nucleotide in exon 2., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-C*03:04:99 differs from HLA-C*03:04:01:01 by one nucleotide in exon 5., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*35:501 differs from HLA-B*35:02:01:01 by three nucleotides in exon 2., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*51:328 differs from HLA-B*51:01:01:01 in exon 2 at position 241 by a single non-synonymous mutation., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-DRB1*13:306 differs from HLA-DRB1*13:02:01:01 in exon 2 in codon 84 by a single coding change., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-B*46:85 differs from HLA-B*46:01:01:01 in exon 3 at position 560 by a single non-synonymous mutation., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-A*69:01:04 differs from HLA-A*69:01:01:01 in exon 2 at position 336 by a single synonymous mutation., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug-induced cutaneous adverse reactions., Methods: A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug-induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes., Results: HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome ( p = 5.63 × 10 -15 ). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group ( p = 1.02 × 10 -5 ) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls ( p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association., Conclusions: HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)