mRNA COVID-19 疫苗接种不会加重多发性硬化症的症状或引发神经抗体反应。
mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis.
机构信息
From the Neuroimmunology and Multiple Sclerosis Unit (Y.B., D.E., S.L., R.R.G., M.A., S.A., J.M.C.-M., M.G., A.H., E.M.-H., M.S., T.A., J.D., A.S.), Hospital Clinic de Barcelona, and Universitat de Barcelona; Neurommunology Program, Fundació de Recerca Clinic Barcelona-IDIBAPS (Y.B., S.L., R.R.G., M.A., E.A., M.A., E.C., J.M.C.-M., E.F., M.G., E.M.-H., G.O.-C., M.R., L.S., M.S., E.S., T.A., J.D., A.S.), Barcelona; Neuromuscular Diseases Unit, Neurology Department (C.L., L.M.-A., C.T.-I., N.V.-F., L.Q.), Hospital de Sant Pau, Barcelona; Centro para la Investigación en Red en Enfermedades Raras (CIBERER) (C.L., M.G., C.T.-I., J.D., L.Q.), Madrid; Department of Immunology (N.E., R.R.G.), Hospital Clinic de Barcelona; Department of Preventive Medicine and Epidemiology (M.A., A.V.), Hospital Clinic de Barcelona, Spain; Department of Neurology (E.F.), School of Medicine, Pontificia Universidad Católica de Chile, Santiago de Chile; Pediatric Neurology Unit (G.O.-C.), Hospital Parc Taulí de Sabadell, Barcelona; Infectious Diseases Unit, Department of Internal Medicine, (J.L.-C., A.R.) Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona; Immunology Department (L.M.-M.), Sant Pau, Institut de Recerca del Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona; Department of Pediatrics, and Infectious Diseases Department (C.F.), Institut de Recerca Pediàtrica Hospital de Sant Joan de Déu, Esplugues de Llobregat, Barcelona; Pediatric Neuroimmunology Unit, Department of Neurology (S.J.D.), Sant Joan de Déu Children´s Hospital (T.A), University of Barcelona, Spain; Department of Neurology, (J.D.) Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Catalan Institute for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2023 Sep 7;10(6). doi: 10.1212/NXI.0000000000200163. Print 2023 Nov.
BACKGROUND AND OBJECTIVE
In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens.
METHODS
This was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine. Blood samples were obtained before the first dose (T1), 1 month after the first dose (T2), 1 month after the second dose (T3), and 6 (T4), 9 (T5), and 12 (T6) months after the first dose. Patients were assessed for the immune-specific response, annualized relapse rate (ARR), and antibodies to onconeuronal, neural surface, glial, ganglioside, and nodo-paranodal antigens.
RESULTS
Among 454 patients studied, 390 had MS (22 adolescents) and 64 OIND; the mean (SD) age was 44 (14) years; 315 (69%) were female; and 392 (87%) were on disease-modifying therapies. Antibodies to the receptor-binding domain were detected in 367 (86%) patients at T3 and 276 (83%) at T4. After a third dose, only 13 (22%) of 60 seronegative patients seroconverted, and 255 (92%) remained seropositive at T6. Cellular responses were present in 381 (93%) patients at T3 and in 235 (91%) patients at T6 including all those receiving anti-CD20 therapies and in 79% of patients receiving fingolimod. At T3 (429 patients) or T6 (395 patients), none of the patients had developed CNS autoantibodies. Seven patients had neural antibodies that were already present before immunization (3 adult patients with MS had MOG-IgG, 2 with MG and 1 with MS had neuronal cell surface antibodies [unknown antigen], and 1 with MS had myelin antibody reactivity [unknown antigen]. Similarly, no antibodies against PNS antigens were identified at T3 (427 patients). ARR was lower in MS and not significantly different in patients with OIND. Although 182 (40%) patients developed SARS-CoV-2 infection, no cases of severe COVID-19 or serious adverse events occurred.
DISCUSSION
In this study, mRNA COVID-19 vaccination was safe and did not exacerbate the autoimmune disease nor triggered neural autoantibodies or immune-mediated neurologic disorders. The outcome of patients who developed SARS-CoV-2 infection was favorable.
背景与目的
在多发性硬化症（MS）患者中，对潜在疾病恶化或引发其他自身免疫性疾病的担忧导致了疫苗犹豫。我们评估了 MS 患者和其他炎症性神经病（OIND）患者在接受 mRNA 疫苗后的体液和 T 细胞对 SARS-CoV-2 的反应、疾病活动的变化以及针对中枢或外周神经系统抗原的抗体的产生。
方法
这是一项前瞻性的 1 年纵向观察研究，纳入了 MS 患者和接受 mRNA 疫苗的其他炎症性神经病患者作为对照组。在第 1 剂疫苗前（T1）、第 1 剂疫苗后 1 个月（T2）、第 2 剂疫苗后 1 个月（T3）、第 6 个月（T4）、第 9 个月（T5）和第 12 个月（T6）采集血样。评估患者的免疫特异性反应、年复发率（ARR）以及针对神经原性、神经表面、神经胶质、神经节苷脂和神经节-旁末梢抗原的抗体。
结果
在 454 例研究患者中，390 例为 MS（22 例为青少年），64 例为 OIND；平均（SD）年龄为 44（14）岁；315 例（69%）为女性；392 例（87%）正在接受疾病修正治疗。在 T3 时，367 例（86%）患者检测到针对受体结合域的抗体，在 T4 时，276 例（83%）患者检测到。在接受第 3 剂疫苗后，仅 60 例血清阴性患者中的 13 例（22%）转为血清阳性，在 T6 时，255 例（92%）仍为血清阳性。在 T3 时，381 例（93%）患者和 T6 时 235 例（91%）患者出现细胞反应，包括所有接受抗 CD20 治疗的患者和 79%接受 fingolimod 治疗的患者。在 T3（429 例患者）或 T6（395 例患者）时，均未发现患者产生中枢神经系统自身抗体。有 7 例患者在免疫前就已存在神经抗体（3 例 MS 成年患者有 MOG-IgG，2 例 MG 和 1 例 MS 患者有神经元细胞表面抗体[未知抗原]，1 例 MS 患者有髓鞘抗体反应[未知抗原]）。同样，在 T3（427 例患者）也未发现针对 PNS 抗原的抗体。MS 患者的 ARR 较低，OIND 患者的 ARR 无显著差异。尽管有 182 例（40%）患者发生 SARS-CoV-2 感染，但无严重 COVID-19 或严重不良事件发生。
讨论
在这项研究中，mRNA COVID-19 疫苗是安全的，不会加重自身免疫性疾病，也不会引发神经自身抗体或免疫介导的神经疾病。发生 SARS-CoV-2 感染的患者的结局是有利的。
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