Laura Y L Kummer, Laura Fernández Blanco, Christine Kreher, Amélie Bos, Lisan H Kuijper, Niels J M Verstegen, Carolien E van de Sandt, Veronique A L Konijn, Mariël C Duurland, Charlotte Menage, Tineke Jorritsma, Maurice Steenhuis, Ruth R Hagen, Jet van den Dijssel, Rivka de Jongh, Tom Ashhurst, Marit J van Gils, Juan J Garcia-Vallejo, Mathieu Claireaux, Eileen W Stalman, Koos P J van Dam, Luuk Wieske, Laura Boekel, Gertjan Wolbink, Sander W Tas, Theo Rispens, Taco W Kuijpers, Filip Eftimov, Sija Marieke van Ham, Anja Ten Brinke
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This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.</p><p><strong>Methods: </strong>In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3-6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.</p><p><strong>Results: </strong>Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. 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引用次数: 0
摘要
目的：甲氨蝶呤（MTX）是治疗类风湿性关节炎（RA）最常用的药物之一。然而，人们对 MTX 治疗对细胞免疫反应的影响仍不甚了解。这引发了人们对这些患者易受新发感染和接种疫苗后的脆弱性的担忧：在本研究中，我们调查了MTX治疗对免疫介导的炎症性疾病患者B细胞和CD4 T细胞SARS-CoV-2疫苗接种反应的影响。研究对象包括 18 名接受 MTX 单药治疗的 RA 患者和两名银屑病关节炎患者，以及 10 名未接受免疫抑制治疗的 RA 患者和 29 名健康对照者。在两次接种 SARS-CoV-2 信使 RNA 疫苗 7 天和 3-6 个月后，对 CD4 T 细胞和 B 细胞反应进行了分析。使用高维流式细胞仪分析新鲜全血，使用活化诱导标记测定法测量抗原特异性 CD4 T 细胞，使用尖峰探针研究抗原特异性 B 细胞：结果：接种两次 SARS-CoV-2 疫苗七天后，MTX 治疗患者和对照组的 B 细胞和 T 细胞总数相似。此外，尖峰特异性 B 细胞频率未受影响。值得注意的是，在使用 MTX 的患者中，抗原特异性 CD4 T 细胞的频率降低，并且与抗 RBD IgG 抗体密切相关。这些结果表明，CD4 T细胞活性的降低可能会导致MTX治疗患者的疫苗抗体反应变慢：综上所述，MTX 治疗可降低疫苗诱导的 CD4 T 细胞活化，这与抗体反应较低有关：NL8900.
Methotrexate treatment hampers induction of vaccine-specific CD4 T cell responses in patients with IMID.
Objectives: Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.
Methods: In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3-6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.
Results: Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.
Conclusion: Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.
期刊介绍：
RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.
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