Grupo de Investigación en Cardiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain.
Servicio de Cardiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC)-CIBERCV, Sergas Universidade da Coruña (UDC), A Coruña, Spain.
PLoS One. 2019 Jul 23;14(7):e0219345. doi: 10.1371/journal.pone.0219345. eCollection 2019.
One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR.
Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR.
We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients.
We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.
心脏移植（HT）中涉及的主要问题之一是抗体介导的排斥反应（AMR）。AMR 的许多方面仍未得到解决，包括其病因、诊断和治疗。在这个项目中，我们假设 HT 患者中涉及 B 细胞生物学的基因变异可以为 AMR 提供诊断和预后信息。
通过下一代测序分析了 46 名 HT 患者（23 名有 AMR，23 名无 AMR）中 61 个与 B 细胞生物学相关的基因中的遗传变异。
我们在 ITGA4 基因中发现了 3 个单核苷酸多态性（c.1845G>A、c.2633A>G 和 c.2883C>T），这些多态性构成了 AGT-ITGA4 单倍型。该单倍型与 AMR 的发生有关。此外，与对照患者中的参考 GAC 单倍型相比，携带 AGT-ITGA4 单倍型的 AMR 患者的血清样本中整合素 α-4 水平较低。
我们可以得出结论，与 B 细胞生物学相关的基因中的多态性可能在 AMR 的发展中起重要作用。事实上，ITGA4 基因中的 AGT 单倍型可能会增加 AMR 的风险。
