Objective: To investigate, in detail, the effects of rituximab (RTX), an off-label drug for treating multiple sclerosis (MS) disease on preventing and/or ameliorating experimental autoimmune encephalomyelitis (EAE).
Methods: Using bioinformatics analysis of publicly available transcriptomics data, we determined the accumulation of B cells, plasma cells and T cells in different compartments of multiple sclerosis patients (MS) and healthy individual brains. Based on these observations and on the literature search, we dosed RTX in EAE mice either orally, or injected intraperitoneally (IP). The latter route was used either prophylactically (asymptomatic stage; upon the induction of the disease), or therapeutically (acute stage; upon the appearance of the first sign of the disease). Further, we used RTX as a preventive drug either as a single agent or in combination with other routes of administration.
Results: Because no complete recovery was observed when RTX was used prophylactically or therapeutically, we devised another protocol of injecting this drug before the onset of the disease and designated this regiment as prevention. We demonstrated that the 20 μg/mouse prevention completely reduced the EAE clinical score, impaired infiltration of T and B cells into the perivascular space of mice brains, along with inhibiting the inflammation and demyelination. However, the 5 and 10 μg/mouse doses although reduced all aspects of inflammation in these mice, their effects were not as potent as the 20 μg/mouse RTX dose. Finally, we combined the 5 μg/mouse prevention treatment with either the prophylactic or therapeutic regimen and observed a robust effect.
Conclusion: We observed that combinatorial regimens resulted in further reduction of inflammation, T and B cell extravasation into the brains of EAE mice and improved the re-myelination.

Keywords: rituximab, inflammation, prevention, prophylactic, therapeutic, T cells, B cells, in silico, bioinformatics, immunohistochemistry


中文翻译：

---

利妥昔单抗预防实验性自身免疫性脑脊髓炎 (EAE) 的发展：与预防性、治疗性或组合方案的比较

目的：详细研究利妥昔单抗（RTX），一种治疗多发性硬化（MS）疾病的超说明书药物对预防和/或改善实验性自身免疫性脑脊髓炎（EAE）的作用。
方法：通过对公开可用的转录组学数据进行生物信息学分析，我们确定了多发性硬化症患者 (MS) 和健康个体大脑不同隔室中 B 细胞、浆细胞和 T 细胞的积累。基于这些观察和文献检索，我们在 EAE 小鼠中口服或腹膜内 (IP) 注射 RTX。后一种途径用于预防性（无症状阶段；在疾病诱发时）或治疗性（急性期；在疾病的第一个迹象出现时）。此外，我们使用 RTX 作为一种预防药物，既可以作为单一药剂，也可以与其他给药途径联合使用。
结果：由于在预防性或治疗性使用 RTX 时未观察到完全恢复，我们设计了另一种在疾病发作前注射这种药物的方案，并将该方案指定为预防方案。我们证明，20 μg/小鼠预防完全降低了 EAE 临床评分，T 和 B 细胞浸润到小鼠大脑血管周围空间受损，同时抑制炎症和脱髓鞘。然而，5 和 10 μg/小鼠剂量虽然减少了这些小鼠炎症的所有方面，但它们的效果不如 20 μg/小鼠 RTX 剂量有效。最后，我们将 5 μg/小鼠的预防治疗与预防性或治疗性方案相结合，并观察到了强大的效果。
结论：我们观察到组合方案导致炎症、T 和 B 细胞外渗到 EAE 小鼠大脑中的进一步减少，并改善了髓鞘再生。

关键词：利妥昔单抗，炎症，预防，预防，治疗，T细胞，B细胞，计算机，生物信息学，免疫组织化学