Light Chain Restriction in Proximal Tubules-Implications for Light Chain Proximal Tubulopathy.
Light Chain Restriction in Proximal Tubules-Implications for Light Chain Proximal Tubulopathy.
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DOI：
10.3389/fmed.2022.723758
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发表时间：
2022
影响因子：
3.9
通讯作者：
Amann K
中科院分区：
文献类型：
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作者：
Büttner-Herold M;Krieglstein N;Chuva T;Minuth K;Pfister F;Daniel C;Klewer M;Büttner A;Ferrazzi F;Bertz S;Amann K
单克隆丙种球蛋白病 (MG) 会引起各种肾病，即使在缺乏多发性骨髓瘤或 B 细胞非霍奇金淋巴瘤的诊断标准的情况下，也可能足以进行细胞减灭治疗。本研究的目的是更好地了解近曲小管中轻链 (LC) 限制或晶体 (LC-R/C) 在 LC 诱导的肾病谱中的重要性。对具有 B 细胞恶液质病史的 320 个肾脏标本组成的连续队列进行了表征。特别关注近端小管、管状晶体或便秘的免疫组织化学 LC 限制以及超微结构发现。进行补充细胞培养实验以评估 LC 浓度在产生 LC 限制中的作用。在四分之一的分析病例中 (81/316) 发现了近端小管中的轻链限制或晶体，并且 70.4% (57/81) 与另一种 LC 诱发的疾病相关，尤其是 LC 管型肾病 (cast-NP) 和间质性骨髓瘤浸润。 11.1% (9/81) 观察到 LC 限制，但没有明显的急性肾小管损伤迹象。当排除伴有管型 NP 的病例时，与其余病例相比，LC-R/C 与肾功能较差无关。除了晶体之外，浑浊的溶酶体在超微结构水平上与 LC-R/C 显着相关。总之，LC-R/C 很常见，并且与cast-NP 密切相关，可能表明高负载的克隆 LC 是造成这种现象的原因，这一现象得到了在细胞培养物中人为产生 LC 限制的观察结果的支持。这以及亚组中缺乏显着的肾小管损伤意味着 LC-R/C 部分是一种肾小管运输现象，而不是一个独立的疾病过程。
Monoclonal gammopathy (MG) causes various nephropathies, which may suffice for cytoreductive therapy even in the absence of diagnostic criteria for multiple myeloma or B-cell non-Hodgkin lymphoma. The aim of this study was to better understand the significance of light chain (LC) restriction or crystals (LC-R/C) in proximal tubules in the spectrum of LC-induced nephropathies. A consecutive cohort of 320 renal specimens with a history of B-cell dyscrasia was characterized. Special attention was paid to immunohistochemical LC restriction in proximal tubules, tubular crystals or constipation, and ultrastructural findings. Complementary cell culture experiments were performed to assess the role of LC concentrations in generating LC restriction. Light chain restriction or crystals in proximal tubules was found in a quarter of analyzed cases (81/316) and was associated with another LC-induced disease in 70.4% (57/81), especially LC cast-nephropathy (cast-NP) and interstitial myeloma infiltration. LC restriction without significant signs of acute tubular injury was observed in 11.1% (9/81). LC-R/C was not associated with inferior renal function compared to the remainder of cases, when cases with accompanying cast-NP were excluded. Besides crystals, cloudy lysosomes were significantly associated with LC-R/C on an ultrastructural level. In summary, LC-R/C is frequent and strongly associated with cast-NP, possibly indicating that a high load of clonal LC is responsible for this phenomenon, supported by the observation that LC restriction can artificially be generated in cell culture. This and the lack of significant tubular injury in a subgroup imply that in part LC-R/C is a tubular trafficking phenomenon rather than an independent disease process.