Division of Anatomic Pathology, Beaumont Laboratories, Beaumont Health , Royal Oak, MI, USA.
Department of Pathology, University of South Alabama , Mobile, AL, USA.
Ultrastruct Pathol. 2020 Nov 20;44(4-6):387-394. doi: 10.1080/01913123.2020.1841349. Epub 2020 Nov 1.
I and animal models of monoclonal light chain-associated renal diseases are limited. The VkMYC transgenic model with multiple myeloma in 50-70 weeks old mice with renal involvement has been reported before, but detailed renal pathologic changes have not been well documented. This study fully investigated pathologic changes in the kidneys of VkMYC transgenic model using light microscopy, immunofluorescence stains for kappa and lambda light chains, and electron microscopy. Compared to the kidneys of wild-type mice, the kidneys of transgenic mice showed either mesangial segmental expansion, some with associated hypercellularity, and/or thrombotic obstruction of glomerular capillaries. The glomeruli revealed stronger lambda staining than kappa light chain staining. Six out of 12 kidneys from transgenic mice showed abundant electron-dense deposits when examined ultrastructurally. The deposits were located in glomerular capillary lumina in three cases. Large luminal and subendothelial deposits were characterized by randomly disposed microtubular structures measuring up to 16 nm in diameter, with overall features most consistent with cryoglobulins. In summary, about 50% of kidneys from the Vk*MYC mice with myeloma had features most consistent with monoclonal cryoglobulinemic glomerulopathy.
我和单克隆轻链相关性肾脏疾病的动物模型有限。以前曾报道过 50-70 周龄携带有多发性骨髓瘤的 VkMYC 转基因小鼠模型存在肾脏受累,但详细的肾脏病理变化尚未得到很好的记录。本研究通过光镜、κ 和 λ 轻链免疫荧光染色以及电子显微镜,充分研究了 VkMYC 转基因模型的肾脏病理变化。与野生型小鼠的肾脏相比,转基因小鼠的肾脏表现为系膜节段性扩张,有些伴有细胞增多和/或肾小球毛细血管血栓阻塞。肾小球显示出比 κ 轻链染色更强的 λ 染色。在超微结构检查时,12 只转基因小鼠的 6 只肾脏中发现了丰富的电子致密沉积物。在 3 例中,沉积物位于肾小球毛细血管腔中。大的管腔和内皮下沉积物的特征是随机排列的微管结构,直径达 16nm,其总体特征与冷球蛋白血症最一致。总之,约 50%的多发性骨髓瘤 Vk*MYC 小鼠的肾脏具有与单克隆冷球蛋白血症性肾小球病最一致的特征。