干扰素 β-1a 治疗可促进多发性硬化症患者对 SARS-CoV-2 mRNA 疫苗的反应。
Interferon Beta-1a treatment promotes SARS-CoV-2 mRNA vaccine response in multiple sclerosis subjects.
机构信息
Neurological Clinic and Stroke Unit, "A. Cardarelli" Hospital, Via A. Cardarelli 9, 80131, Naples, Italy; Multiple Sclerosis Center, "A. Cardarelli" Hospital, Via A. Cardarelli 9, 80131, Naples, Italy.
Neurological Clinic and Stroke Unit, "A. Cardarelli" Hospital, Via A. Cardarelli 9, 80131, Naples, Italy.
出版信息
Mult Scler Relat Disord. 2022 Feb;58:103455. doi: 10.1016/j.msard.2021.103455. Epub 2021 Dec 18.
BACKGROUND
Several concerns exist on the immunogenicity of SARS-CoV-2 vaccines in multiple sclerosis (MS) subjects due to their immunomodulating disease modifying therapies (DMTs). Here we report a comparison of the humoral response to BNT162b2-mRNA coronavirus (COVID)-19 vaccine and the immunological phenotype in a cohort of 125 MS subjects undergoing different DMTs, with no history of SARS-CoV-2 infection.
METHODS
We collected serum and blood samples at the first day of vaccine (T0) and 21 days after the second vaccine dose (T1) from 125 MS subjects, undergoing eight different DMTs. Sera were tested using the Elecsys anti-SARS-CoV-2-IgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgG titres from MS subjects were compared with 24 age- and sex-matched healthy controls (HC). Percentage and absolute number of B and T lymphocytes were evaluated by cytofluorimetric analysis in the same study cohort.
RESULTS
When compared with SARS-CoV-2 IgG levels in HC (n = 24, median 1089 (IQR 652.5-1625) U/mL), we observed an increased secretion of SARS-CoV-2 IgG in interferon-beta 1a (IFN)-treated MS subjects (n = 22, median 1916 (IQR 1024-2879) U/mL) and an impaired humoral response in MS subjects undergoing cladribine (CLAD) (n = 10, median 396.9 (IQR 37.52-790.9) U/mL), fingolimod (FTY) (n = 19, median 7.9 (IQR 4.8-147.6) U/mL) and ocrelizumab (OCRE) (n = 15, median 0.67 (IQR 0.4-5.9) U/mL) treatment. Moreover, analysis of geometric mean titre ratio (GMTR) between different DMT's groups of MS subjects revealed that, when compared with IFN-treated MS subjects, intrinsic antibody production was impaired in teriflunomide (TERI)-, natalizumab (NAT)-, CLAD-, FTY- and OCRE-, while preserved in DMF- and GA-treated MS subjects.
CONCLUSION
Humoral response to BNT162b2-mRNA-vaccine was increased in IFN-treated MS subjects while clearly blunted in those under CLAD, FTY and OCRE treatment. This suggests that the DMTs could have a key role in the protection from SARS-CoV-2 related disease and complication in MS subjects, underlying a novel aspect that should be considered in the selection of the most appropriate therapy under COVID-19 pandemic.
背景
由于多发性硬化症（MS）患者的免疫调节疾病修正治疗（DMT），人们对 SARS-CoV-2 疫苗的免疫原性存在一些担忧。在此，我们报告了在 125 名接受不同 DMT 且无 SARS-CoV-2 感染史的 MS 患者队列中，比较 BNT162b2-mRNA 冠状病毒（COVID-19）疫苗的体液反应和免疫表型。
方法
我们从 125 名接受八种不同 DMT 的 MS 患者中，在疫苗接种的第一天（T0）和第二次接种疫苗后 21 天（T1）采集血清和血液样本。使用 Elecsys 抗 SARS-CoV-2-IgG 检测试剂盒检测血清中针对 SARS-CoV-2 刺突蛋白的 IgG 抗体。将 MS 患者的抗刺突 IgG 滴度与 24 名年龄和性别匹配的健康对照（HC）进行比较。在同一研究队列中，通过流式细胞术分析评估 B 和 T 淋巴细胞的百分比和绝对数量。
结果
与 HC 中 SARS-CoV-2 IgG 水平（n=24，中位数 1089（IQR 652.5-1625）U/mL）相比，我们观察到接受干扰素-β 1a（IFN）治疗的 MS 患者（n=22，中位数 1916（IQR 1024-2879）U/mL）中 SARS-CoV-2 IgG 的分泌增加，而接受氯巴占（CLAD）（n=10，中位数 396.9（IQR 37.52-790.9）U/mL）、芬戈莫德（FTY）（n=19，中位数 7.9（IQR 4.8-147.6）U/mL）和奥瑞珠单抗（OCRE）（n=15，中位数 0.67（IQR 0.4-5.9）U/mL）治疗的 MS 患者的体液反应受损。此外，对不同 DMT 的 MS 患者组的几何平均滴度比（GMTR）进行分析，结果表明与 IFN 治疗的 MS 患者相比，TERI、NAT、CLAD、FTY 和 OCRE 治疗的 MS 患者的固有抗体产生受损，而 DMF 和 GA 治疗的 MS 患者的固有抗体产生未受损。
结论
BNT162b2-mRNA 疫苗接种后，IFN 治疗的 MS 患者的体液反应增强，而 CLAD、FTY 和 OCRE 治疗的 MS 患者的体液反应明显减弱。这表明 DMT 在保护 MS 患者免受 SARS-CoV-2 相关疾病和并发症方面可能发挥关键作用，这是在 COVID-19 大流行期间选择最合适治疗方法时应考虑的一个新方面。
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