Chu Bin, Wang Yu-Tong, Lu Min-Qiu, Shi Lei, Gao Shan, Fang Li-Juan, Xiang Qiu-Qing, Bao Li
Department of Hematology, Jishuitan Hospital, Beijing 100096, China.
Department of Hematology, Jishuitan Hospital, Beijing 100096, China E-mail
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021 Aug;29(4):1195-1202. doi: 10.19746/j.cnki.issn.1009-2137.2021.04.027.
To investigate the expression of CD319 and CD269 in plasma cells of patients with multiple myeloma (MM) and the feasibility of using CD319 instead of CD38 as a gating antigen in immunophenotyping and minimal residual disease (MRD) monitoring.
The expression levels of CD319 and CD269 antigens in clonal bone marrow plasma cells of 387 patients were detected by CD38/CD138 gating strategy with 8-color flow cytometry, and the stability of antigens was also analyzed, and the sensitivity and correlation of two different gating strategies employing CD319/CD138 and CD38/CD138 were compared as well. The control group consisted of 53 cases with non-malignant blood disease matched by age and sex.
Monoclonal plasma cells were detected in 303 of 387 MM patients, among which 277 cases (91.42%) were positive for CD269, and all cases were positive for CD319 (100%). In newly diagnosed MM (NDMM) and recurrent refractory MM (RRMM) patients, the expression levels of CD269 were 97.53% (0-99.92%) and 94.96% (0.22%-99.99%), respectively, while levels of CD319 were 99.90% (87.77%-100%) and 99.78% (63.12%-100%), respectively. The expression levels of CD269 and CD319 in the control group were 97.00% (77.00%-100%) and 100% (89.00%-100%), respectively. There were no significant differences in the expression levels of CD269 and CD319 among NDMM, RRMM and the control group. Patients acquiring therapeutic effects were divided into complete remission (CR) group, very good partial response (VGPR) group and partial response (PR) group. Gating with CD38/CD138, median MRD values were 0.76% (0-1.88%), 0.77% (0-4.96%) and 1.75% (0.09%-10.90%) in the three groups, respectively, while gating with CD319/CD138, median MRD values were 0.57% (0.18%-1.96%), 1.07% (0.12%-4.85%) and 1.77% (0.08%-8.22%), respectively. There was no significant difference in MRD level by the two gating strategies, but a good correlation between the two (r=0.808, P<0.05). In addition, in 4 patients treated by CD38 monoclonal antibody (DARA), the expression level of CD38 was observed to be down-regulated or even negative after treatment. When the MRD level was very low, CD38/CD138 gating resulted in false MRD, while CD319/CD138 gating resulted in MRD.
CD319 and CD269 express stably and continuously in plasma cells of MM patients at different disease stages. CD319 can be used as an alternative of CD38 for immunophenotyping and MRD detection, especially for MRD detection after DARA treatment, while CD269 is suitable for detection before BCMA-CAR-T treatment.
探讨多发性骨髓瘤（MM）患者浆细胞中CD319和CD269的表达情况，以及在免疫表型分析和微小残留病（MRD）监测中使用CD319替代CD38作为门控抗原的可行性。
采用8色流式细胞术的CD38/CD138门控策略检测387例患者克隆性骨髓浆细胞中CD319和CD269抗原的表达水平，分析抗原稳定性，并比较采用CD319/CD138和CD38/CD138两种不同门控策略的敏感性及相关性。对照组为53例年龄和性别匹配的非恶性血液病患者。
387例MM患者中检测到单克隆浆细胞303例，其中277例（91.42%）CD269阳性，所有病例CD319均阳性（100%）。新诊断MM（NDMM）和复发难治性MM（RRMM）患者中，CD269表达水平分别为97.53%（0 - 99.92%）和94.96%（0.22% - 99.99%），而CD319表达水平分别为99.90%（87.77% - 100%）和99.78%（63.12% - 100%）。对照组中CD269和CD319表达水平分别为97.00%（77.00% - 100%）和100%（89.00% - 100%）。NDMM、RRMM与对照组之间CD269和CD319表达水平无显著差异。获得治疗效果的患者分为完全缓解（CR）组、非常好的部分缓解（VGPR）组和部分缓解（PR）组。采用CD38/CD138门控时，三组患者的MRD中位数分别为0.76%（0 - 1.88%）、0.77%（0 - 4.96%）和1.75%（0.09% - 10.90%），而采用CD319/CD138门控时，MRD中位数分别为0.57%（0.18% - 1.96%）、1.07%（0.12% - 4.85%）和1.77%（0.08% - 8.22%）。两种门控策略的MRD水平无显著差异，但两者相关性良好（r = 0.808，P < 0.05）。此外，在4例接受CD38单克隆抗体（DARA）治疗的患者中，观察到治疗后CD38表达水平下调甚至阴性。当MRD水平极低时，CD38/CD138门控导致MRD假阴性，而CD319/CD138门控可检测到MRD。
CD319和CD269在MM患者不同疾病阶段的浆细胞中稳定持续表达。CD319可替代CD38用于免疫表型分析和MRD检测，尤其适用于DARA治疗后的MRD检测，而CD269适用于BCMA - CAR - T治疗前的检测。
