Department of Rheumatology, Goethe University, Frankfurt am Main, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
RMD Open. 2023 Aug;9(3). doi: 10.1136/rmdopen-2023-003094.
To evaluate the potential of immunosuppressed patients to mount B-cell and T-cell responses to COVID-19 booster vaccination (third vaccination).
Patients with primary immunodeficiency (PID), immune-mediated inflammatory diseases (IMIDs) on CD20-depleting treatment with rituximab (RTX), or IMIDs treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biological disease-modifying antirheumatic drug (bDMARDs) were included and assessed before (baseline visit (BL)) and 2, 4 and 8 weeks after COVID-19 booster vaccination. Serum B-cell responses were assessed by antibody levels against SARS-CoV-2 spike protein (anti-spike IgG antibody (S-AB)) and a surrogate virus neutralisation test (sVNT). T-cell responses were assessed by an interferon gamma release assay (IGRA).
Fifty patients with PID (n=6), treated with RTX therapy (n=13), or treated with csDMARDs/bDMARDs (n=31) were included. At BL, anti-S-AB titres in PID and csDMARD/bDMARD-treated patients were low (although significantly higher than RTX patients); measures of B-cell-mediated response increased significantly after booster vaccination. In the RTX cohort, low BL anti-S-AB and sVNT values did not improve after booster vaccination, but patients had significantly elevated IGRA responses post booster vaccination compared with the other groups. csDMARD/bDMARD-treated patients showed the highest BL values in all three assays with greater increases in all parameters after booster vaccination compared with patients with PID.
Patients with IMID on therapeutic B-cell depletion have low anti-S-AB and sVNT values before and after booster vaccination but show significantly higher levels of IGRA compared with other immunosuppressed patients, suggesting an underlying mechanism attempting to compensate compromised humoral immunity by upregulating T-cell responsiveness. PID appears to have a stronger impact on antiviral immune response than csDMARD/bDMARD treatment.
评估免疫抑制患者对 COVID-19 加强疫苗接种（第三次接种）产生 B 细胞和 T 细胞反应的潜力。
纳入原发性免疫缺陷（PID）患者、接受利妥昔单抗（RTX）治疗的免疫介导炎症性疾病（IMIDs）患者、接受传统合成疾病修饰抗风湿药物（csDMARDs）或生物疾病修饰抗风湿药物（bDMARDs）治疗的 IMIDs 患者，并在 COVID-19 加强疫苗接种前（基础访视（BL））和接种后 2、4 和 8 周进行评估。通过针对 SARS-CoV-2 刺突蛋白的抗体水平（抗刺突 IgG 抗体（S-AB））和替代病毒中和试验（sVNT）评估血清 B 细胞反应。通过干扰素γ释放试验（IGRA）评估 T 细胞反应。
纳入 6 例 PID 患者（n=6）、13 例接受 RTX 治疗的患者和 31 例接受 csDMARDs/bDMARDs 治疗的患者。BL 时，PID 和 csDMARD/bDMARD 治疗患者的抗-S-AB 滴度较低（尽管明显高于 RTX 患者）；加强疫苗接种后 B 细胞介导反应的测量值显著增加。在 RTX 队列中，BL 时低的抗-S-AB 和 sVNT 值在加强疫苗接种后并未改善，但与其他组相比，加强疫苗接种后患者的 IGRA 反应显著升高。csDMARD/bDMARD 治疗患者在所有三种检测中均显示出最高的 BL 值，与 PID 患者相比，加强疫苗接种后所有参数的增加均更大。
接受治疗性 B 细胞耗竭的 IMID 患者在加强疫苗接种前后的抗-S-AB 和 sVNT 值较低，但与其他免疫抑制患者相比，IGRA 水平显著升高，表明一种潜在机制试图通过上调 T 细胞反应来补偿受损的体液免疫。PID 对抗病毒免疫反应的影响似乎大于 csDMARD/bDMARD 治疗。
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