利妥昔单抗治疗过程中复发视神经脊髓炎谱系疾病患者外周血淋巴细胞亚群特征分析

Characteristics of peripheral blood lymphocyte subsets in patients with relapsed neuromyelitis optica spectrum disorder during rituximab treatment

目的通过分析利妥昔单抗(RTX)治疗期间复发视神经脊髓炎谱系疾病(NMOSD)患者外周血淋巴细胞亚群特征,明确不同淋巴细胞亚群对NMOSD复发的影响。方法收集中国人民解放军总医院神经内科自2018年8月至2023年8月收治的76例外周血水通道蛋白4-IgG阳性NMOSD患者使用RTX治疗期间的175次淋巴细胞亚群监测数据,根据数据采集时患者是否处于复发状态将数据分为复发组(n=26)和非复发组(n=149)。通过两样本t检验或Mann-Whitney U检验比较2组数据对应的RTX使用时间间隔及淋巴细胞亚群差异,并通过点二列相关分析初步探讨各淋巴细胞亚群及RTX使用时间间隔与NMOSD患者复发之间的相关性。结果复发组RTX使用时间间隔较未复发组明显延长[10.00(6.73,14.37)月vs.7.27(6.30,9.10)月],CD3-CD56^(+)自然杀伤淋巴细胞百分比较未复发组明显偏低[10.72%(7.06%,15.34%)vs.13.85%(9.42%,20.13%)],而CD19^(+)B淋巴细胞百分比较未复发组明显升高[7.41%(1.18%,15.70%)vs.3.55%(0.38%,8.74%)],差异均有统计学意义(P<0.05)。RTX使用时间间隔、CD3-D19^(+)B淋巴细胞与NMOSD是否复发之间存在正相关关系(r=0.363,P<0.001;r=0.218,P=0.004),CD3-CD56^(+)自然杀伤淋巴细胞与NMOSD是否复发之间存在负相关关系(r=-0.193,P=0.011)。结论RTX使用时间间隔延长增加NMOSD复发风险;CD3-CD56^(+)自然杀伤淋巴细胞、CD19^(+)B淋巴细胞可能参与NMOSD患者的疾病状态调控。

Objective To analyze the characteristics of peripheral blood lymphocyte subsets in patients with relapsed neuromyelitis optica spectrum disorder(NMOSD)during rituximab(RTX)treatment and to clarify the influence of these lymphocyte subsets in NMOSD relapse.Methods The monitoring data of lymphocyte subsets(175 times)in 76 patients diagnosed as having aquaporin-4-immunoglobulin G(AQP4-IgG)-seropositive NMOSD during RTX treatment at Department of Neurology,General Hospital of Chinese People's Liberation Army from August 2018 to August 2023 were collected.A relapse group(n=26)and a non-relapse group(n=149)were divided based on states at data collection(relapse or not).Two-sample t-test or Mann-Whitney U test were used to compare the differences in RTX administration intervals and lymphocyte subsets between the 2 groups.Additionally,a point biserial correlation analysis was performed to investigate the correlations of lymphocyte subsets and RTX administration intervals with NMOSD relapse.Results The relapse group had significantly longer RTX administration intervals(10.00[6.73,14.37]months vs.7.27[6.30,9.10]months),statistically lower percentage of CD3-CD56^(+)natural killer lymphocytes(10.72%[7.06%,15.34%]vs.13.85%[9.42%,20.13%]),and significantly higher CD19^(+)B lymphocytes(7.41%[1.18%,15.70%]vs.3.55%[0.38%,8.74%])than the non-relapse group(P<0.05).Positive correlations were noted between RTX administration intervals and NMOSD relapse and between CD3-D19^(+)B lymphocytes and NMOSD relapse(r=0.363,P<0.001;r=0.218,P=0.004);negative correlation was noted between CD3-CD56^(+)NK lymphocytes and NMOSD relapse(r=-0.193,P=0.011).Conclusion Extended RTX administration interval can increase NMOSD relapse;CD3-CD56^(+)natural killer lymphocytes and CD19^(+)B lymphocytes may regulate the disease states of NMOSD patients.