Effect of low-dose rituximab treatment on T- and B-cell lymphocyte imbalance in refractory myasthenia gravis

We aimed to explore the effects of low-dose rituximab (RTX) on circulating T- and B-cell lymphocytes and the improvement of clinical symptoms in refractory myasthenia gravis (MG) patients. Fifteen patients with refractory MG were treated with a low dose of 600 mg RTX and were evaluated by serial-clinical scales, flow cytometry of peripheral blood T and B cells, and antibody titer before and after six months of RTX treatment. The quantitative MG score (QMGS), manual muscle testing (MMT), MG-related activities of daily living (MG-ADL) and MG-specific quality-of-life (QOL) were significantly improved and the average steroid-dosage reduction was 40% (p = .001) in refractory MG patients at six months after RTX infusion. Compared to eighteen non-refractory MG patients and eighteen Healthy controls, our study showed that the frequencies of circulating regulatory B cells (Bregs) and regulatory T cells (Tregs) were significantly lower and the expression of B-cell activating factor receptors (BAFF-Rs) was greater in refractory MG patients without RTX treatment. Importantly, 600-mg RTX was sufficient to deplete B cells and maintain low B-cell counts for up to six months after infusion. Additionally, a low dose of RTX further increased the frequencies of Tregs. Hence, there is an immune imbalance in circulating T-and B-cell lymphocytes in refractory MG patients compared to non-refractory MG patients. We conclude that remarkable T- and B-cell lymphocyte imbalance exists in refractory MG. Low-dose RTX can improve myasthenic symptom and deplete B cells and increase Tregs%.

我们旨在探讨低剂量利妥昔单抗（RTX）对难治性重症肌无力（MG）患者循环T细胞和B细胞淋巴细胞的影响以及临床症状的改善情况。15例难治性MG患者接受了600mg低剂量RTX治疗，并在RTX治疗前后6个月通过系列临床量表、外周血T细胞和B细胞的流式细胞术以及抗体滴度进行评估。在RTX输注6个月后，难治性MG患者的定量重症肌无力评分（QMGS）、手动肌力测试（MMT）、MG相关日常生活活动（MG - ADL）和MG特异性生活质量（QOL）均显著改善，平均类固醇剂量减少了40%（p = 0.001）。与18例非难治性MG患者和18例健康对照相比，我们的研究表明，在未接受RTX治疗的难治性MG患者中，循环调节性B细胞（Bregs）和调节性T细胞（Tregs）的频率显著较低，B细胞活化因子受体（BAFF - Rs）的表达较高。重要的是，600mg RTX足以耗竭B细胞，并在输注后长达6个月内维持低B细胞计数。此外，低剂量RTX进一步增加了Tregs的频率。因此，与非难治性MG患者相比，难治性MG患者的循环T细胞和B细胞淋巴细胞存在免疫失衡。我们得出结论，难治性MG中存在显著的T细胞和B细胞淋巴细胞失衡。低剂量RTX可以改善肌无力症状，耗竭B细胞并增加Tregs的百分比。