SARS-CoV-2 疫苗在接受 DMARDs 治疗的类风湿关节炎（RA）患者中的有效性：通过抗体和 T 细胞应答来确定。
Effectiveness of SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on DMARDs: as determined by antibody and T cell responses.
机构信息
Rheumatology, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK
Leeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
出版信息
RMD Open. 2022 Mar;8(1). doi: 10.1136/rmdopen-2021-002050.
OBJECTIVES
To assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs).
METHODS
This prospective study recruited 100 patients with RA on a variety of DMARDs for antibody and T cell analysis, pre-vaccination and 4 weeks post-vaccination. Positive antibody response was defined as sera IgG binding to ≥1 antigen. Those that remained seronegative after first vaccination were retested 4 weeks after second vaccination; and if still seronegative after vaccination three. A T cell response was defined an ELISpot count of ≥7 interferon (IFN)γ-positive cells when exposed to spike antigens. Type I IFN activity was determined using the luminex multiplex assay IFN score.
RESULTS
After vaccine one, in patients without prior SARS-CoV-2 exposure, 37/83 (45%) developed vaccine-specific antibody responses, 44/83 (53%) vaccine-specific T cell responses and 64/83 (77%) developed either antibody or T cell responses. Reduced seroconversion was seen with abatacept, rituximab (RTX) and those on concomitant methotrexate (MTX) compared to 100% for healthy controls (p<0.001). Better seroconversion occurred with anti-tumour necrosis factor (TNF) versus RTX (p=0.012) and with age ≤50 (p=0.012). Pre-vaccine SARS-CoV-2 exposure was associated with higher quantitative seroconversion (≥3 antibodies) (p<0.001). In the subgroup of non-seroconverters, a second vaccination produced seroconversion in 54% (19/35), and after a third in 20% (2/10). IFN score analysis showed no change post-vaccine.
CONCLUSION
Patients with RA on DMARDs have reduced vaccine responses, particularly on certain DMARDs, with improvement on subsequent vaccinations but with approximately 10% still seronegative after three doses.
目的
评估类风湿关节炎（RA）患者在使用疾病修饰抗风湿药物（DMARDs）时对 SARS-CoV-2 疫苗的抗体和 T 细胞反应。
方法
这项前瞻性研究招募了 100 名正在使用各种 DMARDs 治疗的 RA 患者，进行抗体和 T 细胞分析，在接种疫苗前和接种疫苗后 4 周进行。阳性抗体反应定义为血清 IgG 与≥1 种抗原结合。首次接种后仍呈血清阴性的患者在第二次接种后 4 周进行复测；如果三次接种后仍呈血清阴性，则进行第三次接种。T 细胞反应定义为当暴露于刺突抗原时，ELISpot 计数≥7 个干扰素（IFN）γ阳性细胞。使用 Luminex 多重测定 IFN 评分来确定 I 型 IFN 活性。
结果
在没有 SARS-CoV-2 既往暴露的患者中，接种疫苗后，83 例患者中有 37 例（45%）产生了针对疫苗的抗体反应，83 例患者中有 44 例（53%）产生了针对疫苗的 T 细胞反应，83 例患者中有 64 例（77%）产生了抗体或 T 细胞反应。与健康对照组 100%相比，阿巴西普、利妥昔单抗（RTX）和同时使用甲氨蝶呤（MTX）的患者的血清转化率降低（p<0.001）。与 RTX 相比，使用抗肿瘤坏死因子（TNF）的患者血清转化率更高（p=0.012），年龄≤50 岁的患者血清转化率更高（p=0.012）。接种疫苗前 SARS-CoV-2 暴露与更高的定量血清转化率（≥3 种抗体）相关（p<0.001）。在未发生血清转化的亚组中，54%（19/35）的患者在第二次接种后发生血清转化，在第三次接种后 20%（2/10）的患者发生血清转化。IFN 评分分析显示接种疫苗后无变化。
结论
使用 DMARDs 的 RA 患者的疫苗反应降低，特别是在某些 DMARDs 治疗下，随后的接种可改善反应，但仍有约 10%的患者在接种三剂后仍呈血清阴性。
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