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Effects of re-augmenting maintenance immunosuppression on post-transplant donor-specific HLA antibodies in liver transplantation.
Transplant Immunology ( IF 1.5 ) Pub Date : 2020-09-10 , DOI: 10.1016/j.trim.2020.101334
Kazuaki Tokodai 1 , Shigehito Miyagi 1 , Wataru Nakanishi 1 , Atsushi Fujio 1 , Toshiaki Kashiwadate 1 , Masafumi Goto 2 , Michiaki Unno 1 , Takashi Kamei 1
Affiliation  

Background

Donor-specific antibodies (DSAs) have various negative short- and long-term effects after organ transplantation. DSAs are prevalent in patients with insufficient immunosuppression; thus, even patients with stable conditions after liver transplantation should be under optimized immunosuppression. However, the effect of re-augmenting immunosuppression therapy for patients with insufficient immunosuppression remains unclear. In this study, we investigated the long-term changes and the effects of immunosuppression (IS) re-augmentation on the DSA status.

Methods

Two DSA screenings were performed in 67 patients during long-term follow-up after liver transplantation. After the first screening, IS re-augmentation was performed in patients with consent. The effects of IS re-augmentation on the DSA status were analyzed using data of the serial DSA screenings. Negative conversion was defined as DSA positivity with MFI > 1000 converted to MFI < 1000. Improvement of DSA status was defined as either a 50% reduction of MFI or negative conversion.

Results

The median interval between the first and second DSA screening was 50 months. Among 67 patients, 43 were positive for DSAs on the first screening. Among these 43 patients, 30 had minimal to no IS therapy at the time of the first screening. Among the 30 patients, IS re-augmentation was conducted in 19. A comparison between the patients with a re-augmented IS and those with a sustained minimized IS showed that the DSA levels significantly decreased in the former (63% (12/19) vs. 18% (2/11), p = 0.02).

Conclusions

The results of this study indicate that post-liver transplant IS re-augmentation had suppressive effects on the DSA status. However, the clinical significance of DSA-negative conversion and/or mean fluorescence intensity reduction needs to be further investigated through histological evaluation and/or graft survival during longer follow-up periods.



中文翻译:

重新增强维持免疫抑制对肝移植中移植后供体特异性HLA抗体的影响。

背景

供体特异性抗体(DSA)在器官移植后具有各种负面的短期和长期影响。DSA普遍存在于免疫抑制不足的患者中。因此,即使肝移植后病情稳定的患者也应处于最佳免疫抑制状态。然而,对于免疫抑制不足的患者,重新加强免疫抑制治疗的效果尚不清楚。在这项研究中,我们调查了长期变化以及免疫抑制(IS)增强对DSA状态的影响。

方法

在肝移植后的长期随访期间对67例患者进行了两次DSA筛查。首次筛查后,同意患者进行IS增强。使用连续DSA筛查的数据分析了IS增强对DSA状态的影响。负转换定义为DSA阳性,MFI> 1000转换为MFI <1000。DSA状态的改善定义为MFI降低50%或负转换。

结果

第一次和第二次DSA筛查之间的中位间隔为50个月。在67例患者中,初筛时43例DSA阳性。在这43例患者中,有30例在初次筛查时几乎没有IS治疗。在30例患者中,有19例进行了IS的增强治疗。对IS增强的患者和IS持续最小化的患者进行比较,发现前者的DSA水平显着降低(63%(12/19) vs. 18%(2/11),p  = 0.02)。

结论

这项研究的结果表明,肝脏移植后IS的再次增强对DSA的状态具有抑制作用。然而,DSA负转换和/或平均荧光强度降低的临床意义需要通过组织学评估和/或较长随访期的移植物存活进一步研究。

更新日期:2020-09-10
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