Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Front Immunol. 2022 Jul 5;13:920333. doi: 10.3389/fimmu.2022.920333. eCollection 2022.
Patients with Inflammatory Bowel Disease (IBD) frequently receive immunomodulating treatment, which may render them at increased risk of an attenuated immune response upon vaccination. In this study, we assessed the effects of different types of commonly prescribed immunosuppressive medications on the serological response after vaccination against SARS-CoV-2 in patients with IBD.
In this prospective observational cohort study, IgG antibody titers against SARS-CoV-2 were measured 2-10 weeks after completion of standard vaccination regimens in patients with IBD. Clinical characteristics, previous history of SARS-CoV-2 infection, type of vaccine (mRNA- or vector-based) and medication use were recorded at the time of sampling. Subsequently, a chemiluminescent microparticle immunoassay was used for the quantitative determination of IgG antibodies against the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2.
Three hundred and twelve (312) patients with IBD were included (172 Crohn's disease [CD] and 140 ulcerative colitis [UC]). Seroconversion (defined as titer of >50 AU/ml) was achieved in 98.3% of patients. Antibody concentrations were significantly lower in patients treated with TNF-α-antagonists . non-users of TNF-α-antagonists (geometric mean [95% confidence interval]: 2204 [1655-2935] . 5002 [4089-6116] AU/ml, <0.001). In multivariable models, use of TNF-α-antagonists (<0.001), vector vaccines (<0.001), age (>50 years) (<0.01) and CD (<0.05) were independently associated with lower anti-SARS-CoV-2 antibody titers. In patients who received mRNA vaccines, users of thiopurines (either prescribed as monotherapy or in combination with biologicals) demonstrated significantly lower antibody titers compared to thiopurine non-users (<0.05).
Despite reassuring findings that most patients with IBD have detectable antibodies after anti-SARS-CoV-2 vaccination, TNF-α-antagonists were found to be strongly associated with an attenuated IgG antibody response after vaccination against SARS-CoV-2, independent of vaccine type, the time elapsed after vaccination and blood sampling, prior SARS-CoV-2 infection and patient age. Patients treated with thiopurines and receiving mRNA-based vaccines demonstrated lower anti-SARS-CoV-2 antibody titers compared with non-users.
患有炎症性肠病（IBD）的患者经常接受免疫调节治疗，这可能使他们在接种疫苗时对免疫反应减弱的风险增加。在这项研究中，我们评估了IBD 患者中常用的免疫抑制药物类型对 SARS-CoV-2 疫苗接种后血清学反应的影响。
在这项前瞻性观察队列研究中，我们在 IBD 患者完成标准疫苗接种方案后 2-10 周测量了针对 SARS-CoV-2 的 IgG 抗体滴度。在采样时记录了临床特征、以前的 SARS-CoV-2 感染史、疫苗类型（mRNA 或基于载体的疫苗）和药物使用情况。随后，使用化学发光微粒子免疫分析法定量测定针对 SARS-CoV-2 刺突蛋白 S1 亚单位受体结合域（RBD）的 IgG 抗体。
共纳入 312 例 IBD 患者（172 例克罗恩病[CD]和 140 例溃疡性结肠炎[UC]）。98.3%的患者血清转换（定义为滴度>50 AU/ml）。TNF-α拮抗剂治疗组的抗体浓度显著较低。TNF-α拮抗剂非使用者（几何均数[95%置信区间]：2204[1655-2935]、5002[4089-6116]AU/ml，<0.001）。在多变量模型中，使用 TNF-α拮抗剂（<0.001）、基于载体的疫苗（<0.001）、年龄（>50 岁）（<0.01）和 CD（<0.05）与较低的抗 SARS-CoV-2 抗体滴度独立相关。在接受 mRNA 疫苗接种的患者中，与硫嘌呤非使用者相比，硫嘌呤（单独或与生物制剂联合使用）使用者的抗体滴度显著较低（<0.05）。
尽管大多数 IBD 患者在接种 SARS-CoV-2 疫苗后可检测到抗体，但我们发现 TNF-α拮抗剂与接种 SARS-CoV-2 疫苗后的 IgG 抗体反应减弱密切相关，这与疫苗类型、接种后和采血时间、既往 SARS-CoV-2 感染和患者年龄无关。接受硫嘌呤治疗并接种基于 mRNA 的疫苗的患者与非使用者相比，抗 SARS-CoV-2 抗体滴度较低。
