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Paternal HLA-Derived Epitopes and Live Birth in Secondary Recurrent Pregnancy Loss: New Insights From a Clinical Trial 继发性复发性妊娠失败中父系 HLA 衍生物表位与活产：临床试验的新发现

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-17 DOI: 10.1111/tan.15723

Maria Christine Krog, Emma T. M. Peereboom, Kirsten Geneugelijk, Benedict M. Matern, Astrid Marie Kolte, Ole Bjarne Christiansen, Rudi Steffensen, Henriette Svarre Nielsen, Eric Spierings

Recurrent pregnancy loss (RPL), defined as two or more pregnancy losses before the 24th week of gestation, affects 1%–3% of women worldwide. Approximately, 40% of RPL cases are secondary RPL (sRPL), where women have given birth before facing pregnancy losses. The underlying causes of RPL remain unclear, but immune-related factors may play a role. Previously, a randomised controlled trial using immunoglobulin (IVIG) in sRPL women with a history of four pregnancy losses performed in our RPL unit did not show significant effects of IVIG treatment overall. Yet, some evidence suggests potential benefits for a subset of sRPL patients. In the cohort used for the randomised controlled trial, we examined the role of maternal HLA class II-presented fetal HLA-derived epitopes in sRPL using the predicted indirectly recognisable HLA epitopes (PIRCHE-II) algorithm. In the placebo group, sRPL mothers with an anti-HLA antibody response had higher PIRCHE-II scores when having a live birth compared with sRPL women who experienced another pregnancy loss. This difference was not observed in the IVIG-treated group. Furthermore, as a proxy for T-cell memory, the number of overlapping peptides between the two paternal haplotypes in couples having live births without treatment displayed a larger number of overlapping peptides. This effect was primarily driven by class II-derived peptides. These results suggest that specific combinations of sRPL mothers and fathers, particularly those with an anti-HLA antibody response, may generate higher PIRCHE-II scores, which could contribute to successful live births. Understanding these immune interactions may provide insights for personalised diagnostic and therapeutic strategies in sRPL.

复发性妊娠流产（RPL）是指在妊娠 24 周前发生两次或两次以上的妊娠流产，全世界有 1%-3%的妇女会受到影响。大约 40% 的复发性妊娠流产病例属于继发性复发性妊娠流产（sRPL），即妇女在面临妊娠流产之前已经生育过。RPL 的根本原因尚不清楚，但与免疫相关的因素可能起了一定作用。此前，我们的 RPL 科室曾对有过四次妊娠失败史的 sRPL 妇女进行了一项使用免疫球蛋白（IVIG）的随机对照试验，结果显示 IVIG 治疗的总体效果并不显著。然而，一些证据表明，部分 sRPL 患者可能从中获益。在用于随机对照试验的队列中，我们使用预测的间接可识别 HLA 表位（PIRCHE-II）算法，研究了母体 HLA 二类表位与胎儿 HLA 衍生表位在 sRPL 中的作用。在安慰剂组中，与再次妊娠失败的 sRPL 妇女相比，具有抗 HLA 抗体反应的 sRPL 母亲在活产时的 PIRCHE-II 评分更高。而 IVIG 治疗组则没有观察到这种差异。此外，作为 T 细胞记忆的代表，在未接受治疗的活产夫妇中，两个父系单倍型之间重叠肽的数量较多。这种效应主要是由 II 类衍生肽驱动的。这些结果表明，sRPL 母亲和父亲的特定组合，尤其是那些具有抗 HLA 抗体反应的组合，可能会产生较高的 PIRCHE-II 分数，从而有助于成功活产。了解这些免疫相互作用可为sRPL的个性化诊断和治疗策略提供启示。

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引用次数: 0

Characterisation of the Novel HLA-DRB1*16:79 Allele Using Short- and Long-Read Sequencing Technologies 利用短程和长程测序技术确定新型 HLA-DRB1*16:79 等位基因的特征

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-17 DOI: 10.1111/tan.15724

Gabriela Andrade, Mayara Cunha, Romulo Vianna, Luís Cristóvão Porto, Danielle Secco

The novel HLA-DRB1*16:79 allele, first described in an individual from Brazil.

新型 HLA-DRB1*16:79 等位基因，首次出现在巴西的一个人身上。

引用次数: 0

Characterisation of the Novel HLA-B*58:139 Allele by Next-Generation Sequencing 通过下一代测序确定新型 HLA-B*58:139 等位基因的特征

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-17 DOI: 10.1111/tan.15721

Qi Li, Nanying Chen, Lina Dong, Wei Zhang, Faming Zhu

HLA-B*58:139 differs from the HLA-B*58:01:01:01 allele by one nucleotide substitution in exon 4.

HLA-B*58:139 与 HLA-B*58:01:01:01 等位基因的区别在于外显子 4 中的一个核苷酸替换。

引用次数: 0

Analysis of KIR and HLA Polymorphism in Chinese Individuals With COVID-19 中国 COVID-19 患者的 KIR 和 HLA 多态性分析

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-04 DOI: 10.1111/tan.15715

Sudan Tao, Xuan You, Paul J. Norman, Katherine M. Kichula, Lina Dong, Nanying Chen, Ji He, Wei Zhang, Faming Zhu

Killer-cell immunoglobulin-like receptor (KIR) interactions with HLA class I have crucial roles in modulating NK cell function in response to viral infections. To explore the correlation between KIR/HLA and susceptibility to SARS-CoV-2 infection, we analysed polymorphism of KIR genes, haplotypes, HLA allotypes, and the interplay between KIR and HLA in individuals diagnosed with COVID-19. Compared to a population control group, we observed a significantly increased frequency of KIR3DL3*00802 in the COVID-19 group. When encoded by the HLA-B gene, the frequency of HLA-Bw4, a ligand for KIR3DL1, was at lower frequency in the COVID-19 group. Additionally, significantly elevated frequencies of KIR-Bx3, KIR3DL3*00301, 3DL3*048, and C1⁺HLA-C were identified in the COVID-19 group before multiple test correction, suggesting associations with susceptibility to SARS-CoV-2 infection. Our findings indicate that the KIR3DL3*00802 allele may be a high-risk factor for SARS-CoV-2 infection, while Bw4 encoded by HLA-B gene may confer protective effects against the infection.

杀伤细胞免疫球蛋白样受体（KIR）与 HLA I 类的相互作用在调节 NK 细胞功能以应对病毒感染方面起着至关重要的作用。为了探索 KIR/HLA 与 SARS-CoV-2 感染易感性之间的相关性，我们分析了 COVID-19 诊断个体中 KIR 基因的多态性、单倍型、HLA 异型以及 KIR 和 HLA 之间的相互作用。与人群对照组相比，我们观察到 COVID-19 组中 KIR3DL3*00802 的频率明显增加。由 HLA-B 基因编码的 HLA-Bw4（KIR3DL1 的配体）在 COVID-19 组中的频率较低。此外，在多重检验校正前，COVID-19 组中 KIR-Bx3、KIR3DL3*00301、3DL3*048 和 C1+HLA-C 的频率明显升高，这表明它们与 SARS-CoV-2 感染的易感性有关。我们的研究结果表明，KIR3DL3*00802等位基因可能是感染SARS-CoV-2的高危因素，而HLA-B基因编码的Bw4可能对感染具有保护作用。

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引用次数: 0

Characterization of the Novel HLA-C*07:01:126 Allele by Sequencing-Based Typing 通过基于测序的分型鉴定新型 HLA-C*07:01:126 等位基因。

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-04 DOI: 10.1111/tan.15713

Vincent Elsermans, Jonathan Visentin, Thibault Pajot, Isabelle Top, Myriam Labalette

HLA-C*07:01:126 differs from HLA-C*07:01:01:01 by one nucleotide substitution in codon 328 in exon 7.

HLA-C*07:01:126 与 HLA-C*07:01:01 的区别在于外显子 7 中密码子 328 的一个核苷酸替换。

引用次数: 0

Characterization of the Novel HLA-A*24:02:169 Allele by Sequencing-Based Typing 通过基于测序的分型鉴定新型 HLA-A*24:02:169 等位基因。

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-04 DOI: 10.1111/tan.15712

Vincent Elsermans, Marine Cargou, Thibault Pajot, Isabelle Top, Myriam Labalette

HLA-A*24:02:169 differs from HLA-A*24:02:01:01 by one nucleotide substitution in codon −23 in exon 1.

HLA-A*24:02:169 与 HLA-A*24:02:01:01 的区别在于外显子 1 中密码子 -23 的一个核苷酸替换。

引用次数: 0

The HLA-C*14:152 Allele Was Identified Using a Next-Generation Sequencing Method 使用下一代测序方法鉴定出 HLA-C*14:152 等位基因。

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-04 DOI: 10.1111/tan.15714

Si-Hwan Kim, John Jeongseok Yang, Heung-Bum Oh

HLA-C*14:152 differs from HLA-C*14:02:01:01 by a non-synonymous nucleotide substitution in exon 5.

HLA-C*14:152 与 HLA-C*14:02:01:01 的区别在于外显子 5 中的一个非同义核苷酸置换。

引用次数: 0

Characterisation of the HLA-DQ alpha eplet 52SK targeting the DQA1*01 alleles family 以 DQA1*01 等位基因家族为目标的 HLA-DQ alpha eplet 52SK 的特征。

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-01 DOI: 10.1111/tan.15700

Magali Devriese, Jar How Lee, Tina Meng, Thoa Nong, Neng Jen Remi Shih, François A. Lemonnier, Hiroko Miyadera, Lisa Giraldo, Cédric Usureau, Olivier Toutirais, Dave Lowe, Jean Luc Taupin

Eplet 52SK is unique in the HLA eplet registry as targeting the whole family of DQA1*01 alleles. It is proposed as an antibody-verified eplet but has not been validated enough to deserve this label. Especially, confusion can occur with reactivity targeting the 52PQ eplet which is present on the DQB1*05 and DQB1*06 alleles families, as DQ molecule stability imposes DQA1*01 to selectively associate with these DQ-β families only. Using two Luminex single antigen (LSA) assays from two vendors, beads bearing DR-α/DQ6 heterodimers, a special build LSA panel of additional DQ beads, and an adsorption/elution strategy relying on cells from deceased donors or recombinant cells solely expressing one DQ antigen, we definitely established the antibody-verified status of eplet 52SK using patients' sera reacting only against the DQ5 and DQ6 beads of the One Lambda LSA panel in routine patients' follow up. We also show that reactivity against this eplet is not a rare event among anti-DQ1 immunisation. This study further strengthens the importance of considering the DQA1 locus in immunological studies of HLA and in organ allocation strategies.

外显子 52SK 在 HLA 外显子登记册中是独一无二的，因为它针对的是整个 DQA1*01 等位基因家族。它被建议作为抗体验证的外显子，但尚未得到足够的验证，因此不值得贴此标签。特别是，由于 DQ 分子的稳定性要求 DQA1*01 只能选择性地与这些 DQ-β 家族结合，因此针对 52PQ 表位的反应性可能会与 DQB1*05 和 DQB1*06 等位基因家族混淆。通过使用两个供应商提供的两种 Luminex 单抗原（LSA）检测方法、带有 DR-α/DQ6 异源二聚体的珠子、由其他 DQ 珠子组成的特殊 LSA 面板，以及依赖于死亡供体细胞或仅表达一种 DQ 抗原的重组细胞的吸附/洗脱策略，我们在常规患者随访中使用仅对 One Lambda LSA 面板中的 DQ5 和 DQ6 珠子产生反应的患者血清，确定了 eplet 52SK 的抗体验证状态。我们还发现，在抗 DQ1 免疫接种中，对该表位的反应并不罕见。这项研究进一步加强了在 HLA 免疫学研究和器官分配策略中考虑 DQA1 位点的重要性。

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引用次数: 0

Characterisation of the novel HLA-C*01:262 allele by sequencing-based typing 通过基于测序的分型鉴定新型 HLA-C*01:262 等位基因的特征。

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-01 DOI: 10.1111/tan.15704

Thibault Pajot, Vincent Elsermans, Joan Bitan, Isabelle Top, Myriam Labalette

HLA-C*01:262 differs from HLA-C*01:02:01:01 by one nucleotide substitution in codon 150 in exon 3.

HLA-C*01:262与HLA-C*01:02:01:01的区别在于外显子3中密码子150的一个核苷酸替换。

引用次数: 0

Detection of the HLA-B*40:78 allele in a Taiwanese individual 在一名台湾人身上检测到 HLA-B*40:78 等位基因。

IF 5.9 4区医学 Q2 CELL BIOLOGY

HLA

Pub Date : 2024-10-01 DOI: 10.1111/tan.15709

Kuo-Liang Yang, Py-Yu Lin

One nucleotide substitution in codon 136 of HLA-B*40:02:01:01 results in a novel allele, HLA-B*40:78.

HLA-B*40:02:01:01的密码子136中的一个核苷酸替换产生了一个新的等位基因--HLA-B*40:78。

引用次数: 0

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