Cardiovascular Research Group, Institute of Biomedical Research of A Coruña (INIBIC), A Coruña University Hospital Complex (CHUAC), Galician Healthcare Service (Sergas), University of Coruña.
Cardiology Service, Institute of Biomedical Research of A Coruña (INIBIC), A Coruña University Hospital Complex (CHUAC), Galician Healthcare Service (Sergas), University of Coruña.
Circ J. 2018 Apr 25;82(5):1351-1359. doi: 10.1253/circj.CJ-17-1320. Epub 2018 Apr 3.
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.
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 subunitα (p.Ile75Val-IL4Rα), which correlated with the development of AMR. Moreover, in the analysis of recipient-donor genotype discrepancies, we identified another SNP, in this case inadenosine deaminase(ADA; p.Val178(p=)), which was related to B-cell biology, associated with the absence of AMR.
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.
心脏移植（HT）是治疗终末期心力衰竭的一种成熟的救生治疗方法。抗体介导的排斥反应（AMR）是 HT 后主要问题之一，因为其诊断复杂，支持治疗的证据不足。补体级联和 B 细胞在 AMR 中起着关键作用，并导致移植物损伤。本研究探讨了供体和供受者配对中与补体途径和 B 细胞生物学相关的基因中的变异在 HT 和 AMR 中的重要性。
在 28 对供受者中，对 112 个基因（51 个补体和 61 个 B 细胞生物学基因）的遗传变异进行了下一代测序分析，其中 14 名受者有 AMR，14 名受者无 AMR。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中发现了供体中的一个单核苷酸多态性（SNP），即白细胞介素 4 受体亚单位α（p.Ile75Val-IL4Rα），它与 AMR 的发生相关。此外，在受者-供者基因型差异的分析中，我们发现了另一个 SNP，在这种情况下，在腺苷脱氨酶（ADA；p.Val178（p=））中，它与 B 细胞生物学有关，与 AMR 的缺失有关。
与 B 细胞生物学相关的供体多态性和受者-供者差异，可能在 AMR 的发展中起重要作用。相比之下，补体途径中的供体或供受者对中似乎没有变异对 AMR 有影响。
