Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Am J Kidney Dis. 2022 Jun;79(6):904-908. doi: 10.1053/j.ajkd.2021.07.021. Epub 2021 Sep 8.
Tubular basement membrane (TBM) deposits are very uncommon in non-lupus membranous nephropathy. We report 5 patients with membranous nephropathy and extensive TBM deposits following allogeneic hematopoietic cell transplant. Patients presented with nephrotic syndrome (3 also had acute kidney injury) late post-transplant in association with chronic graft-versus-host disease (cGVHD). Kidney biopsies revealed global subepithelial and extensive TBM immune complex deposits, accompanied by acute tubular injury (n = 4) and tubulointerstitial inflammation (n = 4). Proteomic analysis of glomeruli in 4 cases identified PLAR in 1, with no significant protein spectra for PLAR, THSD7A, EX1/2, NELL-1, PCDH7, NCAM1, or SEMA3B detected in the remaining 3. On follow-up (for a mean 42 months), 4 patients had complete and 1 partial remission following prednisone and/or rituximab therapy. We propose that membranous nephropathy with extensive TBM deposits is a distinctive clinicopathologic lesion associated with allogeneic hematopoietic cell transplant. Pathogenesis likely involves cGVHD-driven antibodies against glomerular and TBM components, the identity of which remains to be elucidated.
管状基底膜 (TBM) 沉积物在非狼疮性膜性肾病中非常罕见。我们报告了 5 例异基因造血细胞移植后发生膜性肾病和广泛 TBM 沉积物的患者。这些患者在移植后晚期出现肾病综合征(3 例同时伴有急性肾损伤),并伴有慢性移植物抗宿主病 (cGVHD)。肾活检显示广泛的上皮下和 TBM 免疫复合物沉积,伴有急性肾小管损伤(n=4)和肾小管间质性炎症(n=4)。4 例肾小球的蛋白质组学分析在 1 例中鉴定出 PLAR,其余 3 例未检测到 PLAR、THSD7A、EX1/2、NELL-1、PCDH7、NCAM1 或 SEMA3B 的显著蛋白谱。在平均随访 42 个月时,4 例患者在接受泼尼松和/或利妥昔单抗治疗后完全缓解,1 例部分缓解。我们提出,广泛 TBM 沉积物的膜性肾病是一种与异基因造血细胞移植相关的独特临床病理病变。发病机制可能涉及针对肾小球和 TBM 成分的 cGVHD 驱动抗体,其性质仍有待阐明。