Laboratoire d'Immunologie, CHU de Nice, Université Côte d'Azur, Nice, France.
Centre Méditerranéen de Médecine Moléculaire (C3M), INSERM U1065, Université Côte d'Azur, Nice Côte d'Azur University, Archet Hospital, 151, route Saint-Antoine de Ginestière CS 23079 -, 06202, Nice, France.
Neurotherapeutics. 2021 Apr;18(2):938-948. doi: 10.1007/s13311-021-01006-9. Epub 2021 Mar 25.
Myasthenia gravis can be efficiently treated with rituximab but there is no consensus regarding administration and dose schedules in this indication. No marker has yet been described to predict the clinical relapse of patients. Our objective was to identify the B cell subpopulations predicting clinical relapse in patients suffering from generalized myasthenia gravis and treated with rituximab. Clinical and biological data of 34 patients followed between 2016 and 2019 were prospectively collected every 3 months. Using multiparameter flow cytometry, we assessed the percentage in leucocytes of lymphocytes and several B cell subpopulations measured in residual disease conditions. CD19+ were also measured in non-residual disease conditions. Clinical examinations were performed by neurologists using the Osserman score. Clinical relapse occurred in 14 patients (41%). No patients required ICU or ventilatory assistance. The mean improvement of the Osserman score was 17.18 (3-45) after the first rituximab treatment (p < 0.0001). The mean delay between the first rituximab maintenance cycle and clinical relapse was 386.8 days. At the time of relapse, CD27+ increased (p = 0.0006) with AUC = 0.7654, while CD19+ did not. At a threshold of 0.01%, the sensitivity and specificity of CD19+CD27+ were 75.8% and 72.8%, respectively, and the positive and negative predictive values were 28.0% and 95.6%, respectively. The percentage of memory B cells in whole blood cells can accurately predict clinical relapse in myasthenia gravis patients treated with rituximab. This monitoring allows physicians to tailor rituximab administration and to decrease the number of infusions over time.
重症肌无力可以通过利妥昔单抗有效治疗,但在该适应证中,关于给药途径和剂量方案尚未达成共识。目前尚未描述任何标志物来预测患者的临床复发。我们的目的是确定预测接受利妥昔单抗治疗的全身性重症肌无力患者临床复发的 B 细胞亚群。前瞻性收集了 2016 年至 2019 年间随访的 34 例患者的临床和生物学数据,每 3 个月采集一次。使用多参数流式细胞术,我们评估了白细胞中淋巴细胞和残留疾病条件下测量的几种 B 细胞亚群的百分比。还在非残留疾病条件下测量了 CD19+。神经病学家使用 Osserman 评分进行临床检查。14 例患者(41%)发生临床复发。没有患者需要 ICU 或呼吸机辅助。首次利妥昔单抗治疗后,Osserman 评分平均改善 17.18(3-45)(p<0.0001)。首次利妥昔单抗维持周期与临床复发之间的平均时间间隔为 386.8 天。在复发时,CD27+增加(p=0.0006),AUC=0.7654,而 CD19+未增加。当阈值为 0.01%时,CD19+CD27+的灵敏度和特异性分别为 75.8%和 72.8%,阳性和阴性预测值分别为 28.0%和 95.6%。全血细胞中记忆 B 细胞的百分比可以准确预测接受利妥昔单抗治疗的重症肌无力患者的临床复发。这种监测可以使医生调整利妥昔单抗的给药,并随着时间的推移减少输注次数。