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青少年风湿性疾病患者对 mRNA SARS-CoV-2 BNT162b2 疫苗的体液和细胞免疫反应。

Humoral and cellular immune response to mRNA SARS-CoV-2 BNT162b2 vaccine in adolescents with rheumatic diseases.

机构信息

Paediatric Rheumatology Unit, Hospital Infantil La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain.

La Paz Institute of Biomedical Research (IdiPAZ), 28046, Madrid, Spain.

出版信息

Pediatr Rheumatol Online J. 2022 Aug 13;20(1):64. doi: 10.1186/s12969-022-00724-4.

Abstract

BACKGROUND

Data about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question.

OBJECTIVE

To evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group.

METHODS

Adolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (n = 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (n = 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins.

RESULTS

There were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination.

CONCLUSIONS

We conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.

摘要

背景

关于患有风湿性疾病 (RD) 的青少年接种 mRNA SARS-CoV-2 疫苗的安全性和疗效的数据很少,这些患者是否能对疫苗产生足够的免疫反应仍然是一个悬而未决的问题。

目的

评估接受 BNT162b2 疫苗接种的 12 至 18 岁患有 RD 且接受免疫抑制治疗的青少年与健康对照组相比的安全性以及体液和细胞免疫应答。

方法

马德里拉帕斯医院随访的 12 至 18 岁患有 RD 的青少年(n=40)接受 BNT162b2 mRNA 疫苗接种,接种后 3 周进行评估。健康青少年作为对照组(n=24)。通过 IgG 抗刺突抗体测量体液反应,通过 SARS-CoV-2 刺突和 M 蛋白刺激后全血中 IFN-γ 和 IL-2 的数量测量细胞反应。

结果

两组之间在刺突特异性体液或细胞反应方面没有差异(对照组 S 特异性蛋白的中位 IFN-γ 反应;528.80pg/ml 与 RD 患者的 398.44pg/ml,p 0.78,对照组中 IL-2 的中位反应为 635.68pg/ml,RD 患者为 497.30pg/ml,p 0.22)。最常见的诊断是青少年特发性关节炎(26/40,65%),其次是狼疮(6/40,15%)。60%的病例(23/40)接受 TNF 抑制剂治疗,35%(14/40)接受甲氨蝶呤治疗。40%的患者(26/64)有以前的 SARS-CoV-2 感染史,对照组 9 例,RD 患者 17 例,无差异。值得注意的是,70%的感染为无症状。与对照组的无感染史者相比,COVID-19 康复者的 IFN-γ 产生更高(对照组:康复者的中位值为 859pg/ml,而无感染史者为 450pg/ml,p 0.017,RD 患者:康复者为 850pg/ml,无感染史者为 278pg/ml,p 0.024)。接种疫苗后未报告严重不良事件或疾病加重。

结论

我们得出结论,与健康对照组相比,包括 TNF 抑制剂和甲氨蝶呤在内的 RD 青少年的标准治疗方案并未影响 BNT162b2 mRNA 疫苗的体液和细胞免疫应答。与 SARS-CoV-2 的先前接触是免疫反应的最相关因素。

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