Lai Zongshan, Kumar Tripti, Zhao Ran, Li Wei, Kanaan Hassan D, Zhang Ping L, Liu Bei
Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI.
Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Ann Clin Lab Sci. 2019 Sep;49(4):439-447.
Monoclonal gammopathy of renal significance (MGRS) is a state of circulating monoclonal immunoglobulin (Ig) and light chains that cause kidney injury without definite evidence of multiple myeloma (MM). Although chemotherapy is used to treat many variants of MGRS and has been recently recommended, relatively limited clinical validation studies are available. A few transgenic models of MM reveal renal deposition of monoclonal Ig and light chains. We have demonstrated that the XBP1s-transgenic mouse model from early plasma cell dyscrasia to MM reveals monoclonal IgG/kappa deposition at the subendothelial spaces of the glomeruli, mimicking proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Inhibition of a key immune-modulator, gp96/grp94, genetically or pharmacologically results in a significant reduction of plasma cells within the bone marrow and reduced renal deposition of monoclonal IgG and kappa light chain. This article will review the emerging role of and animal models from plasma cell dyscrasia to MM in understanding the renal deposition of monoclonal Ig and light chains, along with its potential treatment strategies.
具有肾意义的单克隆丙种球蛋白病（MGRS）是一种循环单克隆免疫球蛋白（Ig）和轻链的状态，可导致肾损伤，且无明确的多发性骨髓瘤（MM）证据。尽管化疗用于治疗MGRS的多种变体且最近已被推荐，但相对有限的临床验证研究可用。一些MM转基因模型显示了单克隆Ig和轻链的肾沉积。我们已经证明，从早期浆细胞发育异常到MM的XBP1s转基因小鼠模型显示肾小球内皮下空间有单克隆IgG/κ沉积，类似于伴有单克隆免疫球蛋白沉积的增殖性肾小球肾炎。从基因或药理学上抑制关键免疫调节剂gp96/grp94会导致骨髓内浆细胞显著减少，以及单克隆IgG和κ轻链的肾沉积减少。本文将综述从浆细胞发育异常到MM的动物模型在理解单克隆Ig和轻链肾沉积方面的新作用，以及潜在的治疗策略。
