Characteristics and predictive value for graft fibrosis of the complement-binding capacity of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation

Characteristics and predictive value for graft fibrosis of the complement-binding capacity of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation
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DOI:
10.1111/petr.13648
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发表时间:
2019-12-29
影响因子:
1.3
通讯作者:
Kamei, Takashi
Kamei, Takashi
中科院分区:
医学4区
文献类型:
--
作者:
Tokodai, Kazuaki;Miyagi, Shigehito;Kamei, Takashi

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供体特异性HLA抗体(dsa)对器官移植后的短期和长期预后都有不利影响。尽管有证据表明dsa的补体结合能力在肾移植中具有预测能力,但其在肝移植后长期随访中的临床影响尚不清楚。在这项研究中,我们评估了dsa的补体结合能力及其与组织学结果的关系。方法回顾性分析我院1991年7月至2013年10月间接受小儿LT治疗的72例患者。对37例接受肝移植活检的患者进行组织学亚组分析。根据移植物纤维化程度将患者分为两组,评估临床特征。结果抗I类dsa均为c1q阴性。分别在34%和41%的患者中发现了抗dr和抗dq dsa;然而,25例抗dr dsa患者中只有3例显示c1q结合试验阳性,而29例抗dq dsa患者中有25例显示c1q结合能力。具有c1q结合能力的患者的DSA MFI值显著高于无c1q结合能力的患者(P < 0.0001)。补体结合抗dr DSA在两组中均相对少见。关于抗dq DSA,无论补体结合能力如何,纤维化组和非纤维化组之间没有差异。结论抗dr DSA与肝纤维化之间的相关性在本队列中得到了支持,但考虑到补体结合能力,由于低阳性检测,抗dr DSA与肝纤维化之间的相关性没有增强,而是减弱了。需要进一步研究补体结合抗dq DSA与LT组织学结果之间的关系。
Background Donor-specific HLA antibodies (DSAs) have detrimental effects on short- and long-term outcomes after organ transplantation. Despite evidence that the complement-binding capacity of DSAs has predictive power in kidney transplantation, its clinical impact during long-term follow-up after LT remains unclear. In this study, we assessed the complement-binding capacities of DSAs and their association with histological findings. Methods In total, 72 patients who underwent pediatric LT at our institution between July 1991 and October 2013 were retrospectively reviewed. A subgroup analysis of histological findings was performed for 37 subjects who underwent liver graft biopsy. Patients were divided into two groups based on the degree of graft fibrosis, and clinical characteristics were assessed. Results All anti-class I DSAs were C1q-negative. Anti-DR and anti-DQ DSAs were identified in 34% and 41% of patients, respectively; however, only three of 25 patients with anti-DR DSAs exhibited a positive C1q-binding assay, whereas, 25 of 29 anti-DQ DSAs showed C1q-binding capacity. MFI values for DSA were significantly higher for patients with C1q-binding capacity than for those without (P < .0001). Complement-binding anti-DR DSA was relatively rare in both groups. Regarding anti-DQ DSA, there were no differences between fibrosis and non-fibrosis groups, irrespective of complement-binding capacity. Conclusions The association between anti-DR DSA and liver fibrosis, which was supported in this cohort, was not strengthened but rather impaired when accounting for complement-binding capacity due to low positive detection. Further studies of the association between complement-binding anti-DQ DSA and histological findings in LT are needed.