系统性轻链型淀粉样变性异常浆细胞特征分析

Plasma cell characteristics in patients with systemic light-chain amyloidosis

目的:分析系统性轻链型淀粉样变性(AL)患者骨髓克隆性浆细胞数量与免疫表型特征,探索浆细胞数量、表型与疾病风险分层的联系。方法:多参数流式细胞术(MFC)检测AL患者骨髓浆细胞CD19、CD38、CD138、CD56、CD117表达情况及κ、λ轻链限制性,对照组选择同期诊断非AL的具有肾脏意义的单克隆免疫球蛋白血症(MGRS)及多发性骨髓瘤(MM)患者。收集实验室检查结果,观察AL患者临床特征,分析其单克隆浆细胞数量、免疫表型与疾病风险分层的关系。结果:共纳入AL患者119例,对照组非AL的MGRS 49例伴单克隆免疫球蛋白沉积的增生性肾小球肾炎27例,单克隆免疫球蛋白沉积病16例,轻链沉积病3例,重链沉积病2例,轻链重链混合淀粉样变性(AHL)型1例、MM 19例。AL患者有96例(80.7%)骨髓浆细胞检测出轻链限制性,单克隆浆细胞表面CD19、CD56、CD117阳性率分别为10.4%、71.9%、46.9%。与MGRS、MM比较,AL单克隆浆细胞CD117阳性率较高(P=0.001,P<0.001),浆细胞数量高于MGRS(P<0.001)而低于MM(P<0.001)。单克隆浆细胞CD19阴性的AL患者骨髓浆细胞数量高于CD19阳性患者(P=0.013)。结合Mayo分期系统,AL中单克隆浆细胞比例最高的为Ⅳ期0.98%(0.6%,1.37%),最低为Ⅱ期0.53%(0.29%,1.03%),两组间差异有统计学意义(P=0.033);CD117在Ⅳ期患者中阳性率高于Ⅱ、Ⅲ期患者(P=0.032,P=0.021)。结论:AL与MGRS、MM克隆性浆细胞数量及表型存在差异,AL患者Mayo分期等级高的患者克隆性浆细胞负荷及CD117阳性率较高,提示MFC检测AL患者骨髓浆细胞数量及其免疫表型特征,可辅助疾病的诊断、鉴别与疾病风险评估。

Objective:To investigate the number and immunophenotypic characteristics of malignant plasma cells in bone marrow and their relationship with disease risk stratification in patients with primary systemic light chain amyloidosis(AL).Methodology:Using multiparametric flow cytometry(MFC)to measure the expression of CD19,CD38,CD138,CD56,CD117 andκ/λlight chain restriction of plasma cells.The patients with monoclonal gammopathy of renal significance(MGRS)and multiple myloma(MM)were selected as control groups.Laboratory examination results were collected to observe the clinical characteristics of AL patients.Results:A total of 119 AL patients and a control group consist of 49 patients with non-AL MGRS(27 cases of Proliferative glomerulonephritis with monoclonal Ig deposits,16 cases of monoclonal immunoglobulin deposition disease,3 cases of light chain deposition disease,2 cases of heavy chain deposition disease,one case of heavy and light chains amyloidosis)and 19 patients with MM were enrolled in this study.96(80.7%)AL patients cases were found out light chain restriction,the positive expression rate of CD19,CD56,and CD117 on plasma cell surface was 10.4%71.9%and 46.9%,respectively.The number of bone marrow plasma cells in AL patients was higher than that in MGRS patients(P<0.001)and lower than that in MM patients(P<0.001),compared with the latter two,the positive rate of CD117 of monoclonal plasma cells in AL patients was higher(P=0.001,P<0.001).The number of plasma cells in AL patients with CD19 negative on monoclonal plasma cells’surface was higher than that in patients with CD19-positive monoclonal plasma cells(P=0.013).Furthermore,based on Mayo staging system,the highest proportion of monoclonal plasma cells in AL patients was 0.98%(0.6%,1.37%)in stageⅣ,and the lowest was 0.53%(0.29%,1.03%)in stageⅡ.The difference between the two groups was statistically significant(P=0.033).The positive rate of CD117 was higher in stageⅣpatients than in stageⅡandⅢpatients(P=0.032,P=0.021).Conclusion:The number and immunophenotypic characteristics of monoclonal plasma cells in AL patients are different with those in MGRS and MM patients.Besides,AL patients with higher Mayo stage have higher clonal plasma cell load and CD117 positive rate.Altogether,using MFC to detect the number of bone marrow plasma cells and their immunophenotypic characteristics can help diagnosis and risk assessment of AL.