Monoclonal immunoglobulin (MIg) crystalline nephropathies are rare lesions resulting from precipitation of MIgs in the kidney as intracellular or extracellular crystals. We describe a patient with multiple myeloma (IgGλ) and diabetes who presented with nephrotic range proteinuria. Kidney biopsy revealed membranous nephropathy superimposed on diabetic glomerulosclerosis. Glomeruli were negative for PLA2R, THSD7A, and NELL-1. Ultrastructurally, the subepithelial deposits were composed of crystals (ranging from rhomboid to rod to needle shaped), which failed to stain for immunoglobulins by routine immunofluorescence but stained for IgG+λ by paraffin immunofluorescence after pronase digestion. RNA-based immunoglobulin repertoire sequencing performed on bone marrow aspirate identified an IgGλ (γ1) clone, which was highly atypical, combining an extensively mutated (23.6%) Ig heavy chain derived from the IGHV1-24 with low pI and unusual mutations and a light chain derived from an extremely rare germline gene (IGLV10-54). This report expands the pathologic spectrum of MIg crystalline nephropathies by describing a unique case of crystalline nephropathy with IgGλ deposits manifesting as membranous nephropathy.

中文翻译：

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单克隆免疫球蛋白结晶膜性肾病

单克隆免疫球蛋白 (MIg) 结晶性肾病是罕见的病变，是由于 MIg 在肾脏中以细胞内或细胞外晶体的形式沉淀而引起的。我们描述了一位患有多发性骨髓瘤 (IgGλ) 和糖尿病的患者，其表现为肾病范围蛋白尿。肾活检显示膜性肾病叠加糖尿病肾小球硬化。肾小球 PLA2R、THSD7A 和 NELL-1 呈阴性。超微结构观察，上皮下沉积物由晶体组成（从菱形到棒状到针状），常规免疫荧光无法对免疫球蛋白进行染色，但链霉蛋白酶消化后，通过石蜡免疫荧光对IgG+λ进行染色。对骨髓抽吸物进行基于 RNA 的免疫球蛋白库测序，鉴定出 IgGλ (γ1) 克隆，该克隆高度非典型，结合了源自 IGHV1-24 的广泛突变 (23.6%) Ig 重链，具有低 pI 和异常突变以及轻链链源自极其罕见的种系基因（IGLV10-54）。本报告通过描述一例具有 IgGλ 沉积并表现为膜性肾病的结晶性肾病的独特病例，扩展了 MIg 结晶性肾病的病理谱。