Miguel-Garcia A, Matutes E, Tarin F, Garcia-Talavera J, Miguel-Sosa A, Carbonell F, Catovsky D
Department of Haematology, Hospital General Universitario, Valencia, Spain.
J Clin Pathol. 1995 Sep;48(9):835-9. doi: 10.1136/jcp.48.9.835.
To estimate the proportion and nature of the proliferating (Ki67+) circulating lymphocytes in a series of patients with multiple myeloma and monoclonal gammopathy of unknown significance (MGUS) and to correlate this with other clinical and laboratory parameters, using blood from healthy adults as a control. To investigate the extent to which the B and T lymphoid components are involved in progression and/or control of disease.
Blood lymphocytes from 15 patients with multiple myeloma, 10 patients with MGUS and 10 healthy adults were analysed using a sequential double immunoenzymatic staining technique. Antibodies directed against Ki67 were used to detect cells in cycle, CD3, CD4, and CD8 to identify T cells, HLA-Dr as a marker for B cells and activated T cells, and CD11b as a marker for natural killer cells. Polyclonal antibodies directed against the kappa and lambda immunoglobulin light chains were also used to detect B cells.
The proportion of proliferating (Ki67+) lymphocytes was significantly higher in patients with multiple myeloma (6.8 +/- 2.6) and MGUS (3.5 +/- 1.1) compared with the normal controls (1.69 +/- 0.3); this was also true when multiple myeloma and MGUS cases were compared. In multiple myeloma and MGUS over 50% of the Ki67+ cells were activated T lymphocytes (CD3+/HLA-Dr+); a minority (11%) were non-clonal B lymphocytes. In contrast to controls (6.7 +/- 1.9), in patients with multiple myeloma and MGUS the proportion of proliferating T cells expressing CD8 (23.6 +/- 12.5 and 15.3 +/- 7.7, respectively) and CD11b (13 +/- 8.7 and 11.6 +/- 3.9, respectively) was higher. In multiple myeloma there was a positive correlation between the proportion of Ki67+ lymphocytes, beta-2-microglobulin concentrations and disease stage.
Although the number of patients investigated is small, this study suggests that Ki67 expression in blood lymphocytes from patients with multiple myeloma may be a good prognostic indicator for aggressive disease and may help to distinguish multiple myeloma from MGUS. The activated proliferating T cells in these diseases may represent an immunological reaction against the tumour.
以健康成年人血液为对照，评估一系列多发性骨髓瘤和意义未明的单克隆丙种球蛋白病（MGUS）患者中增殖性（Ki67+）循环淋巴细胞的比例和性质，并将其与其他临床和实验室参数相关联。研究B和T淋巴细胞成分在疾病进展和/或控制中的参与程度。
采用序贯双免疫酶染色技术分析15例多发性骨髓瘤患者、10例MGUS患者和10例健康成年人的血液淋巴细胞。使用针对Ki67的抗体检测处于细胞周期的细胞，使用CD3、CD4和CD8鉴定T细胞，使用HLA-Dr作为B细胞和活化T细胞的标志物，使用CD11b作为自然杀伤细胞的标志物。还使用针对kappa和lambda免疫球蛋白轻链的多克隆抗体检测B细胞。
与正常对照组（1.69±0.3）相比，多发性骨髓瘤患者（6.8±2.6）和MGUS患者（3.5±1.1）中增殖性（Ki67+）淋巴细胞的比例显著更高；多发性骨髓瘤和MGUS病例比较时也是如此。在多发性骨髓瘤和MGUS中，超过50%的Ki67+细胞是活化的T淋巴细胞（CD3+/HLA-Dr+）；少数（11%）是非克隆性B淋巴细胞。与对照组（6.7±1.9）相比，在多发性骨髓瘤和MGUS患者中，表达CD8（分别为23.6±12.5和15.3±7.7）和CD11b（分别为13±8.7和11.6±3.9）的增殖性T细胞比例更高。在多发性骨髓瘤中，Ki67+淋巴细胞比例、β2-微球蛋白浓度与疾病分期之间存在正相关。
尽管研究的患者数量较少，但本研究表明，多发性骨髓瘤患者血液淋巴细胞中的Ki67表达可能是侵袭性疾病的良好预后指标，可能有助于将多发性骨髓瘤与MGUS区分开来。这些疾病中活化的增殖性T细胞可能代表针对肿瘤的免疫反应。
