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首页> 外文期刊>Circulation journal >Donor Polymorphisms in Genes Related to B-Cell Biology Associated With Antibody-Mediated Rejection After Heart Transplantation
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Donor Polymorphisms in Genes Related to B-Cell Biology Associated With Antibody-Mediated Rejection After Heart Transplantation

机译：心脏移植后与抗体介导的排斥反应有关的B细胞生物学相关基因的供体多态性

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Background: Heart transplantation (HT) is a well-established lifesaving treatment for endstage cardiac failure. Antibody-mediated rejection (AMR) represents one of the main problems after HT because of its diagnostic complexity and the poor evidence for supporting treatments. Complement cascade and B-cells play a key role in AMR and contribute to graft damage. This study explored the importance of variants in genes related to complement pathway and B-cell biology in HT and AMR in donors and in donor-recipient pairs. Methods?and?Results: Genetic variants in 112 genes (51 complement and 61 B-cell biology genes) were analyzed on next-generation sequencing in 28 donor-recipient pairs, 14 recipients with and 14 recipients without AMR. Statistical analysis was performed with SNPStats, R, and EPIDAT3.1. We identified one single nucleotide polymorphism (SNP) in donors in genes related to B-cell biology, interleukin-4 receptor subunit α (p.Ile75Val- IL4R α), which correlated with the development of AMR. Moreover, in the analysis of recipient-donor genotype discrepancies, we identified another SNP, in this case in adenosine deaminase ( ADA ; p.Val178(p=)), which was related to B-cell biology, associated with the absence of AMR. Conclusions: Donor polymorphisms and recipient-donor discrepancies in genes related to the biology of B-cells, could have an important role in the development of AMR. In contrast, no variants in donor or in donor-recipient pairs in complement pathways seem to have an impact on AMR.
机译：背景：心脏移植（HT）是一种用于晚期心力衰竭的行之有效的救生治疗方法。抗体介导的排斥反应（AMR）是HT治疗后的主要问题之一，因为它的诊断复杂性和支持治疗的证据不充分。补体级联和B细胞在AMR中起关键作用，并导致移植物损伤。这项研究探讨了供体和供体-受体对中与补体途径和B细胞生物学相关的基因在HT和AMR中的重要性。方法和结果：在下一代测序中分析了112个基因（51个补体和61个B细胞生物学基因）的遗传变异，分析了28个供体-受体对，14个有AMR的接受者和14个无AMR的接受者。使用SNPStats，R和EPIDAT3.1进行统计分析。我们在与B细胞生物学相关的基因白细胞介素4受体亚基α（p.Ile75Val-IL4Rα）的供体中鉴定了一个单核苷酸多态性（SNP），这与AMR的发生有关。此外，在分析受体与供体的基因型差异时，我们在腺苷脱氨酶（ADA; p.Val178（p =））中鉴定了另一种SNP，这与B细胞生物学有关，且与AMR缺失有关。 。结论：与B细胞生物学有关的基因中的供体多态性和受体-供体差异可能在AMR的发展中起重要作用。相反，补体途径中供体或供体-受体对中的变体似乎对AMR没有影响。

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