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在接受芬戈莫德治疗的 MS 患者中,抗体滴度是否有助于验证 VZV 疫苗接种后的免疫效果?一项病例系列研究。

Is antibody titer useful to verify the immunization after VZV Vaccine in MS patients treated with Fingolimod? A case series.

机构信息

Multiple Sclerosis Center, Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Italy.

Multiple Sclerosis Center, Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Italy.

出版信息

Mult Scler Relat Disord. 2020 May;40:101963. doi: 10.1016/j.msard.2020.101963. Epub 2020 Jan 20.

Abstract

BACKGROUND

Fingolimod (FTY720, Gilenya) is a second line therapy to treat relapsing MS not responding to first-line treatments and/or with a high disease activity (according to Italian Regulatory authorities). Before starting Fingolimod, patients' immunity to varicella zoster virus (VZV) needs to be assessed and seronegative patients vaccinated. To test susceptibility and response, IgG antibodies are tested after immunization. Since Fingolimod determines a reduction of circulating B lymphocytes and immunoglobulins, we aimed at describing the trend of VZV antibodies in seronegative vaccinated patients with MS before and after treatment.

METHODS

A total of 23 patients vaccinated for VZV before starting Fingolimod treatment, were recruited in this observational retrospective study involving five MS Centers in Campania (Italy). Of these, 12 patients were excluded for missing data. Patients received two doses of Varivax® Vaccine. After vaccination patients were re-tested and were all positive for IgG-VZV. We re-tested IgG-VZV in the same laboratory after a mean time of 2.42 years from Fingolimod therapy start.

RESULTS

During Fingolimod therapy we observed a global reduction of antibody titer and a disappearance in 7/11 patients. Titer disappearance was more probable in patients with lower post-vaccination titer. Of the 7 patients with vanishing IgG-VZV, three suspended Fingolimod for adverse event. In two of them, we observed a reappearance of antibody titer after treatment cessation. In one patient chickenpox infection occurred one year later.

DISCUSSION AND CONCLUSIONS

Our observational study shows that Fingolimod could influence antibody titer probably through its effect on B lymphocytes, but the efficacy of the vaccination should be verified. In conclusion, it is necessary to pay attention to therapies acting on B lymphocytes as they could influence the antibody titer and efficacy of vaccination making the search for other markers of vaccine efficacy desirable such as cell-mediated immunity with proliferation and induction of memory T lymphocytes in response to viral glycoproteins.

摘要

背景

芬戈莫德(FTY720,吉兰雅)是一种二线治疗药物,用于治疗对一线治疗无反应和/或疾病活动度高的复发性多发性硬化症(根据意大利监管机构)。在开始使用芬戈莫德之前,需要评估患者对水痘带状疱疹病毒(VZV)的免疫力,并且对血清阴性患者进行疫苗接种。为了测试易感性和反应性,在免疫接种后测试 IgG 抗体。由于芬戈莫德会导致循环 B 淋巴细胞和免疫球蛋白减少,因此我们旨在描述治疗前和治疗后血清阴性的多发性硬化症疫苗接种患者 VZV 抗体的趋势。

方法

本观察性回顾性研究共纳入了来自意大利坎帕尼亚地区五个 MS 中心的 23 例在开始芬戈莫德治疗前接种 VZV 的患者。其中,12 例患者因数据缺失而被排除。患者接受了两剂 Varivax®疫苗。接种疫苗后,所有患者 IgG-VZV 均转为阳性。在开始芬戈莫德治疗后平均 2.42 年,我们在同一实验室重新检测了 IgG-VZV。

结果

在芬戈莫德治疗期间,我们观察到抗体滴度整体下降,11 例中有 7 例消失。在接种疫苗后滴度较低的患者中,滴度消失的可能性更大。在 7 例 IgG-VZV 消失的患者中,有 3 例因不良反应而停用芬戈莫德。在其中 2 例中,停药后观察到抗体滴度再次出现。在 1 例患者中,一年后发生水痘感染。

讨论和结论

我们的观察性研究表明,芬戈莫德可能通过其对 B 淋巴细胞的作用影响抗体滴度,但疫苗接种的效果仍需验证。总之,需要注意作用于 B 淋巴细胞的治疗方法,因为它们可能会影响抗体滴度和疫苗接种的效果,这使得寻找其他疫苗疗效标志物成为必要,如细胞介导免疫,通过对病毒糖蛋白的增殖和诱导记忆 T 淋巴细胞反应来评估。

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