Fanconi's syndrome induced by a monoclonal Vκ3 light chain in Waldenstrom's macroglobulinemia
Fanconi's syndrome induced by a monoclonal Vκ3 light chain in Waldenstrom's macroglobulinemia
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DOI：
10.1053/j.ajkd.2004.12.020
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发表时间：
2005-04-01
影响因子：
13.2
通讯作者：
Touchard, G
中科院分区：
文献类型：
--
作者：
Bridoux, F;Sirac, C;Touchard, G
范科尼综合征 (FS) 是一种钠依赖性近端小管重吸收疾病，可能使产生游离单克隆轻链 (LC) 的浆细胞疾病复杂化。 FS 经常发生在冒烟性骨髓瘤的情况下，其特征是近端肾小管细胞和恶性浆细胞中存在单克隆 kappa LC 的细胞质结晶内含物。尽管临床和病理表现可能有所不同，包括缺乏晶体形成，但 FS 背后的单克隆 kappa LC 显示出惊人的遗传和生化同质性：它们几乎总是属于 V(kappa)1 变异亚组，并且源自 2 个种系基因 O2/O12 或 O8/O18。它们的可变结构域序列呈现出不寻常的疏水性残基，负责抵抗蛋白水解，从而导致 LC 在近端小管细胞的内吞区室中积聚。我们报告了一名患有缓慢进展的华氏巨球蛋白血症和完全成熟的 FS 的患者，近端肾小管内有单克隆 kappa LC 积聚，但没有可检测到的晶体组织。该 LC 属于不寻常的 V(kappa)3 亚组，源自 L2/L16 种系基因，与之前描述的 FS kappa I LC 没有表现出常见的取代，并且对胰蛋白酶消化敏感。这些数据表明 FS 患者的 kappa LC 的分子和生化特征比最初怀疑的更加异质。 FS 相关浆细胞恶液质的发病机制可能涉及 LC 对内体蛋白水解的抵抗以外的机制。 (c) 2005 年，国家肾脏基金会 (National Kidney Foundation, Inc.)
Fanconi's syndrome (FS) is a disorder of sodium-dependent proximal tubule reabsorption, which may complicate plasma cell disorders producing a free monoclonal light chain (LC). FS often occurs in the setting of smoldering myeloma and features cytoplasmic crystalline inclusions of monoclonal kappa LC in proximal tubular cells and malignant plasma cells. Although the clinical and pathological presentation may vary, including lack of crystal formation, monoclonal kappa LCs that underlie FS show a striking genetic and biochemical homogeneity: they almost always belong to the V(kappa)1 subgroup of variability and originate from 2 germline genes, O2/O12 or O8/O18. Their variable domain sequences present unusual hydrophobic residues, responsible for the resistance to proteolysis, which leads to LC accumulation in the endocytic compartment of proximal tubule cells. We report a patient with slowly progressive Waldenstrom's macroglobulinemia and full-blown FS with accumulation of a monoclonal kappa LC within proximal tubules, but no detectable crystalline organization. This LC, which belonged to the unusual V(kappa)3 subgroup and derived from the L2/L16 germline gene, showed no common substitution with previously described FS kappa I LC and was sensitive to trypsin digestion. These data show that molecular and biochemical characteristics of kappa LCs in patients with FS are more heterogeneous than initially suspected. Mechanisms other than resistance of LCs to endosomal proteolysis probably are involved in the pathogenesis of FS-associated plasma cell dyscrasias. (c) 2005 by the National Kidney Foundation, Inc.