Department of Laboratory Medicine, Hematology and Transfusion Medicine, Lund University, Lund, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Region Skåne, Lund, Sweden.
J Immunol Res. 2022 Jul 28;2022:7561661. doi: 10.1155/2022/7561661. eCollection 2022.
Patients with rheumatoid arthritis (RA) have an increased risk of infections; therefore, immunization against vaccine-preventable diseases is important. Methotrexate (MTX) impairs the antibody response to pneumococcal conjugate vaccine (PCV) in patients with arthritis, and the underlying mechanism is largely unknown. Here, we investigate the potential role of the innate immune system in the faltering antibody response following PCV vaccination in RA patients treated with MTX. Phenotypes of circulating granulocytes and monocytes were analyzed in 11 RA patients treated with MTX, 13 RA patients without disease-modifying antirheumatic drug treatment (0DMARD), and 13 healthy controls (HC). Peripheral blood samples were collected before and 7 days after vaccination. In addition, the MTX group was sampled before initiating treatment. Frequencies of granulocyte and monocyte subsets were determined using flow cytometry. Serotype-specific IgG were quantified using a multiplex bead assay, pre- and 4-6 weeks after vaccination. At baseline, no differences in granulocyte and monocyte frequencies were observed between the groups. Within the MTX group, the frequency of basophils increased during treatment and was higher compared to the HC and 0DMARD groups at the prevaccination time point. MTX patients were categorized into responders and nonresponders according to the antibody response. Before initiation of MTX, there were no differences in granulocyte and monocyte frequencies between the two subgroups. However, following 6-12 weeks of MTX treatment, both the frequency and concentration of monocytes were lower in PCV nonresponders compared to responders, and the difference in monocyte frequency remained after vaccination. In conclusion, the suppressive effect of MTX on monocyte concentration and frequency could act as a biomarker to identify nonresponders to PCV vaccination.
类风湿关节炎（RA）患者感染风险增加；因此，针对可通过疫苗预防的疾病进行免疫接种很重要。甲氨蝶呤（MTX）会损害关节炎患者对肺炎球菌结合疫苗（PCV）的抗体反应，其潜在机制在很大程度上尚不清楚。在这里，我们研究了先天免疫系统在 MTX 治疗的 RA 患者接种 PCV 后抗体反应减弱中的潜在作用。分析了 11 例 MTX 治疗的 RA 患者、13 例未接受疾病修饰抗风湿药物治疗（DMARD）的 RA 患者和 13 例健康对照者（HC）的循环粒细胞和单核细胞表型。在接种疫苗前和接种后 7 天采集外周血样本。此外，MTX 组在开始治疗前采样。使用流式细胞术测定粒细胞和单核细胞亚群的频率。使用多重珠粒测定法在接种前和接种后 4-6 周定量测定血清型特异性 IgG。在基线时，各组间粒细胞和单核细胞频率无差异。在 MTX 组内，在治疗过程中嗜碱性粒细胞的频率增加，并且在接种前时间点比 HC 和 0DMARD 组更高。根据抗体反应将 MTX 患者分为应答者和无应答者。在开始 MTX 治疗之前，两组之间粒细胞和单核细胞频率无差异。然而，在 MTX 治疗 6-12 周后，PCV 无应答者的单核细胞频率和浓度均低于应答者，并且接种后这种单核细胞频率的差异仍然存在。总之，MTX 对单核细胞浓度和频率的抑制作用可作为识别 PCV 接种无应答者的生物标志物。
