Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Department of Immunology and Immunogenetics, Centre Hospitalier Universitaire de Limoges, Limoges, France; Control of the immune response B and lymphoproliferation, CNRS UMR 7276, INSERM UMR 1262, University of Limoges, Centre de référence de l'amylose AL et autres maladies par dépôts d'immunoglobuline monoclonale, Limoges, France.
Am J Kidney Dis. 2024 Jul;84(1):120-125. doi: 10.1053/j.ajkd.2023.11.011. Epub 2024 Jan 23.
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.
单克隆免疫球蛋白（MIg）结晶肾病是一种罕见的病变，其原因是 MIg 在肾脏中沉淀为细胞内或细胞外晶体。我们描述了一位患有多发性骨髓瘤（IgGλ）和糖尿病的患者，其表现为肾病范围的蛋白尿。肾活检显示膜性肾病合并糖尿病肾小球硬化。肾小球 PLA2R、THSD7A 和 NELL-1 均为阴性。超微结构下，上皮下沉积物由晶体组成（呈菱形、杆状到针状），常规免疫荧光染色未能检测到免疫球蛋白，但在蛋白酶消化后石蜡免疫荧光染色显示 IgG+λ。骨髓抽吸物的基于 RNA 的免疫球蛋白库测序鉴定出一个 IgGλ（γ1）克隆，该克隆高度异常，其 Ig 重链来自 IGHV1-24，高度突变（23.6%），pI 低，且存在异常突变，轻链来自一个非常罕见的胚系基因（IGLV10-54）。本报告通过描述一个独特的 IgGλ 沉积表现为膜性肾病的结晶性肾病病例，扩展了 MIg 结晶性肾病的病理谱。
