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人类白细胞抗原抗体和白细胞抗原/杀伤细胞免疫球蛋白样受体基因在肝移植中的重要性。

Importance of human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes in liver transplantation.

机构信息

Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia 30120, Spain.

Department of Legal and Forensic Medicine, Biomedical Research Institute (IMIB), Regional Campus of International Excellence "Campus Mare Nostrum," Faculty of Medicine, University of Murcia, Murcia 30120, Spain.

出版信息

World J Gastroenterol. 2023 Feb 7;29(5):766-772. doi: 10.3748/wjg.v29.i5.766.

Abstract

Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance, which is described by eventual imbalances or deregulation in the balance of cytokines, mediators, effectors, and regulatory cells in the complex milieu of the liver. In this section, we will comment on the importance of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor (KIR) genotypes in the evolution of liver transplantation. Thus, HLA compatibility, viral infections, and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival. There have been reports of increased risk of acute and chronic rejection with ductopenia, faster graft fibrosis, biliary problems, poorer survival, and even autoimmune hepatitis when DSAs are present in the recipient. Higher mean fluorescence intensity (MFI) values of the DSAs and smaller graft size were associated with poorer patient outcomes, implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods, according to the investigators. Similarly, in a combined kidney-liver transplant, a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment. The renal graft was lost owing to antibody-mediated rejection (AMR). The HLA antigens expressed by the transplanted liver graft influenced antibody elimination. Pathologists are increasingly diagnosing AMR in liver transplants, and desensitization therapy has even been employed in situations of AMR, particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex. In conclusion, after revealing the negative impacts of DSAs with high MFI, pretransplant virtual crossmatch techniques may be appropriate to improve evolution; however, they may extend cold ischemia periods by requiring the donor to be typed.

摘要

许多机制被提出来解释肝脏耐受的假设状态,这是由肝脏复杂环境中的细胞因子、介质、效应物和调节细胞的平衡最终失衡或失调所描述的。在这一节中,我们将评论供体特异性抗人类白细胞抗原(HLA)抗体(DSA)以及 HLA 和杀伤细胞免疫球蛋白样受体(KIR)基因型的相容性和配对在肝移植中的重要性。因此,HLA 相容性、病毒感染和 HLA-C/KIR 组合都与肝移植排斥和存活有关。有报道称,在受体内存在 DSA 时,急性和慢性排斥反应的风险增加、移植物纤维化更快、胆道问题、存活率降低,甚至发生自身免疫性肝炎。DSA 存在时,DSA 的平均荧光强度(MFI)值较高和移植物较小与患者预后较差有关,这意味着应根据研究者的建议,考虑对具有预先形成的 DSA 的高危患者选择移植物和脱敏方法。同样,在联合肾肝移植中,移植前可见几种 DSA 的表达表明这些抗体对治疗有抵抗力。由于抗体介导的排斥反应(AMR),肾移植物丢失。移植肝脏中表达的 HLA 抗原影响抗体的消除。病理学家越来越多地在肝移植中诊断 AMR,甚至在 AMR 情况下也采用脱敏治疗,特别是在肾肝移植中具有 DSA 和由于 Luminex 导致的高 II 类 MFI 的患者中。总之,在揭示了具有高 MFI 的 DSA 的负面影响后,移植前虚拟交叉配型技术可能适合改善进展;然而,它们可能会通过要求供体进行分型而延长冷缺血期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d656/9932425/684ebfdad75b/WJG-29-766-g001.jpg

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