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Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients
Journal of the American Society of Nephrology ( IF 10.3 ) Pub Date : 2022-01-01 , DOI: 10.1681/asn.2021050715
Yu Ho Lee 1, 2 , Yuki Sato 1, 3 , Mitsuru Saito 4 , Shingo Fukuma 5 , Masaya Saito 6 , Shigenori Yamamoto 1, 3 , Atsushi Komatsuda 6 , Nobuhiro Fujiyama 7 , Shigeru Satoh 7 , Sang-Ho Lee 8 , Peter Boor 9, 10, 11 , Tomonori Habuchi 4 , Jürgen Floege 10 , Motoko Yanagita 1, 12
Affiliation  

Background

Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the effects of TLTs on future graft function using our histologic TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs.

Methods

Serial protocol biopsy samples (0 hour, 1, 6, and 12 months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells.

Results

Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy, and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared with patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pretransplantation rituximab treatment dramatically attenuated the development of stage II TLTs.

Conclusions

TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation.



中文翻译:

协议活检中晚期第三淋巴组织与肾移植受者的进行性移植物功能障碍有关

背景

第三淋巴组织 (TLT) 是在慢性发炎器官中发现的异位淋巴组织。尽管研究记录了移植肾中 TLT 的形成,但这些 TLT 的临床相关性仍存在争议。我们使用我们的组织学 TLT 成熟阶段以及 TLT 和 Banff 病理评分之间的关​​联检查了 TLT 对未来移植物功能的影响。我们还分析了 TLT 发展的风险因素。

方法

回顾性分析了 214 名接受活体肾移植的患者的无排斥反应的系列活检样本(0 小时、1 个月、6 个月和 12 个月)。TLT 被定义为具有增殖迹象的淋巴细胞聚集体,其分期由滤泡树突状细胞的缺失(I 期)或存在(II 期)决定。

结果

只有 4% 的患者在 0 小时活检时表现出 TLT。在 1 个月的活检时患病率增加到近 50%,然后在 12 个月内略有增加。晚期 II 期 TLT 的比例逐渐增加,在 12 个月的活检时达到 19%。与没有 TLT 或 I 期 TLT 的患者相比,II 期 TLT 的存在与移植后肾功能下降的更高风险相关。II 期 TLT 在 12 个月时与更严重的肾小管炎和间质纤维化/肾小管萎缩相关,并且独立于间质炎症的程度预测移植物功能较差。移植前利妥昔单抗治疗显着减弱了 II 期 TLT 的发展。

结论

TLT 通常存在于临床稳定的移植肾中。晚期 II 期 TLT 与进行性移植物功能障碍相关,与间质炎症无关。

更新日期:2021-12-31
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