青少年特发性关节炎患者在使用和停用抗 TNF 药物期间接种 Tdap 加强针是安全且具有免疫原性的。

Tdap booster to adolescents with juvenile idiopathic arthritis on and off anti-TNF agents is safe and immunogenic.

机构信息

Unit of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.

Research Laboratory, Division of Pediatric Infectious Diseases, Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.

出版信息

Vaccine. 2021 Feb 12;39(7):1165-1172. doi: 10.1016/j.vaccine.2020.12.071. Epub 2021 Jan 19.

DOI:10.1016/j.vaccine.2020.12.071

PMID:33478788

Abstract

INTRODUCTION

The response to vaccines in juvenile idiopathic arthritis (JIA) patients on and off anti-tumor necrosis factor (anti-TNF) agents remains highly discussed. There are no published studies on the immune response following a Tdap booster dose in JIA patients so far.

OBJECTIVE

To evaluate the immune response and safety after a Tdap booster in JIA patients and in healthy adolescents.

METHODS

Nineteen adolescents with JIA according to the ILAR criteria on anti-TNF medication, 19 adolescents with JIA off anti-TNF medication, and 27 healthy adolescents (control group) were compared after a Tdap booster. Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole-cell pertussis, and supernatants were assessed for cytokines by xMAP.

RESULTS

The three groups showed a similar frequency of adverse events. There was no disease reactivation after the Tdap booster. Tetanus, diphtheria and pertussis antibodies showed a significant response when D0 and D14 concentrations were compared in both JIA groups and controls. Over time, a different pattern of response to the Tdap booster was observed among the groups for tetanus antibodies (p = 0.005) but not for diphtheria and pertussis antibodies. In contrast to the protection attained for tetanus and diphtheria, in the three groups, not all individuals showed pertussis seroconversion at either D14 or D28. In addition, the seroconversion of three subjects with JIA on anti-TNF medication was not maintained at D28. JIA patients off anti-TNF showed a higher percentage of naive CD8 + T cells (p = 0.007) and central memory CD8 + cells (p = 0.003) and a lower percentage of effector CD8 + T cells (p = 0.003) and NK cell numbers (p = 0.018) than the control group. The JIA group off anti-TNF medication had fewer B lymphocytes than both the JIA group on anti-TNF medication and the control group (p = 0.016). Cellular immunity to Bordetella pertussis showed that IFNγ levels were significantly lower in both JIA groups than in the control group (p = 0.003), IL10 levels were higher in the JIA off anti-TNF group (p = 0.009), IL17A and IL5 levels were lower in the JIA on anti-TNF group than in the control group (p = 0.018 and p = 0.016, respectively); however, an increase in IFNγ (p = 0.008), IL17A (p = 0.030) and TNFα (p = 0.041) levels was observed at D14 in both patient groups. Both JIA groups showed higher levels of IL21 than the control group (p = 0.023).

CONCLUSION

We conclude that individuals with JIA on or off anti-TNF agents showed a good response to a booster dose for the three antigens studied in the absence of major adverse events and without the reactivation of the disease.

摘要

简介

在使用抗肿瘤坏死因子（anti-TNF）药物和停用 anti-TNF 药物的青少年特发性关节炎（JIA）患者中，疫苗的反应仍然存在很大争议。目前尚无关于 JIA 患者接种 Tdap 加强针后免疫反应的研究。

目的

评估 JIA 患者和健康青少年接种 Tdap 加强针后的免疫反应和安全性。

方法

19 名符合 ILAR 标准的 JIA 患者（使用 anti-TNF 药物）、19 名 JIA 患者（停用 anti-TNF 药物）和 27 名健康青少年（对照组）接受 Tdap 加强针后进行比较。评估不良反应和疾病活动度。通过流式细胞术进行淋巴细胞免疫表型分析。通过 ELISA 评估破伤风、白喉和百日咳毒素抗体；用全细胞百日咳菌刺激全血，通过 xMAP 评估上清液中的细胞因子。

结果

三组不良反应发生率相似。加强针后无疾病复发。两组 JIA 患者和对照组在 D0 和 D14 浓度时破伤风、白喉和百日咳抗体均有显著反应。随着时间的推移，三组间对 Tdap 加强针的反应模式不同，破伤风抗体存在差异（p=0.005），但白喉和百日咳抗体无差异。与破伤风和白喉获得的保护不同，三组中并非所有个体在 D14 或 D28 时均出现百日咳抗体血清转换。此外，三名使用 anti-TNF 药物的 JIA 患者的血清转换在 D28 时并未维持。停用 anti-TNF 药物的 JIA 患者表现出更高比例的幼稚 CD8+T 细胞（p=0.007）和中央记忆 CD8+细胞（p=0.003），以及更低比例的效应 CD8+T 细胞（p=0.003）和 NK 细胞数量（p=0.018），与对照组相比。与使用 anti-TNF 药物的 JIA 组相比，停用 anti-TNF 药物的 JIA 组的 B 淋巴细胞更少（p=0.016）。对博德特氏菌百日咳的细胞免疫反应表明，两组 JIA 患者的 IFNγ水平均显著低于对照组（p=0.003），JIA 停用 anti-TNF 组的 IL10 水平更高（p=0.009），JIA 用 anti-TNF 组的 IL17A 和 IL5 水平均低于对照组（p=0.018 和 p=0.016）；然而，两组患者在 D14 时 IFNγ（p=0.008）、IL17A（p=0.030）和 TNFα（p=0.041）水平均升高。两组 JIA 患者的 IL21 水平均高于对照组（p=0.023）。