Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study
Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study
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DOI：
10.1182/blood-2018-09-872028
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发表时间：
2019-02-07
期刊：
影响因子：
20.3
通讯作者：
Bridoux, Frank
中科院分区：
文献类型：
--
作者：
Joly, Florent;Cohen, Camille;Bridoux, Frank
单克隆免疫球蛋白沉积病（MIDD）是B细胞克隆性疾病的一种罕见并发症，其定义为单克隆轻链（LCDD）、重链（HCDD）或两者（LHCDD）的刚果红阴性沉积。MIDD是一种以肾脏受累为特征的全身性疾病，但其肾外表现的描述却很少被关注。此外，致病性免疫球蛋白沉积的机制以及与肾脏和患者生存相关的因素尚不明确。我们回顾性研究了255例经活检证实的LCDD患者（n = 212）（包括单纯LCDD [n = 154]，LCDD伴管型肾病（CN）[n = 58]），HCDD（n = 23）或LHCDD（n = 20）。血液学诊断为单克隆丙种球蛋白病的肾脏意义在64%和症状性骨髓瘤在34%。LCCD和CN患者的肾脏表现为急性肾损伤，其他类型的患者为慢性肾小球疾病，其中35%有症状性肾外（主要是肝脏和心脏）受累。18个致病性LC的测序显示可变结构域互补决定区的高等电点值，可能占组织沉积。在接受化疗的169例患者中（58%以硼替佐米为基础），67%实现了血清游离轻链（FLC）缓解，包括52%的非常好的部分缓解（VGPR）或以上。62例患者（36%）出现肾脏缓解，所有患者均达到血液学缓解。FLC反应>= VGPR和无严重间质纤维化是肾反应的独立预测因素。这项研究强调了MIDD中肾外表现的意外频率。快速诊断和获得深部FLC反应是预后的关键因素。
Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of B-cell clonal disorders, defined by Congo red negative-deposits of monoclonal light chain (LCDD), heavy chain (HCDD), or both (LHCDD). MIDD is a systemic disorder with prominent renal involvement, but little attention has been paid to the description of extrarenal manifestations. Moreover, mechanisms of pathogenic immunoglobulin deposition and factors associated with renal and patient survival are ill defined. We retrospectively studied a nationwide cohort of 255 patients, with biopsy-proven LCDD (n = 212) (including pure LCDD [n = 154], LCDD with cast nephropathy (CN) [n = 58]), HCDD (n = 23), or LHCDD (n = 20). Hematological diagnosis was monoclonal gammopathy of renal significance in 64% and symptomatic myeloma in 34%. Renal presentation was acute kidney injury in patients with LCCD and CN, and chronic glomerular disease in the other types, 35% of whom had symptomatic extrarenal (mostly hepatic and cardiac) involvement. Sequencing of 18 pathogenic LC showed high isoelectric point values of variable domain complementarity determining regions, possibly accounting for tissue deposition. Among 169 patients who received chemotherapy (bortezomib-based in 58%), 67% achieved serum free light chain (FLC) response, including very good partial response (VGPR) or above in 52%. Renal response occurred in 62 patients (36%), all of whom had achieved hematological response. FLC response >= VGPR and absence of severe interstitial fibrosis were independent predictors of renal response. This study highlights an unexpected frequency of extrarenal manifestations in MIDD. Rapid diagnosis and achievement of deep FLC response are key factors of prognosis.