利妥昔单抗可抑制自身免疫性疾病患者对 COVID-19 疫苗的 B 细胞应答，但不影响 T 细胞应答。
Rituximab Impairs B Cell Response But Not T Cell Response to COVID-19 Vaccine in Autoimmune Diseases.
机构信息
Hôpital Bicêtre, AP-HP, FHU CARE, and Université Paris-Saclay, INSERM UMR 1184, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Paris, France.
Hôpital Bicêtre, AP-HP, FHU CARE, Paris, France.
出版信息
Arthritis Rheumatol. 2022 Jun;74(6):927-933. doi: 10.1002/art.42058. Epub 2022 Mar 29.
OBJECTIVE
Antibody response to the messenger RNA (mRNA) COVID-19 vaccine has been shown to be diminished in rituximab (RTX)-treated patients. We undertook this study to compare humoral and T cell responses between healthy controls, patients with autoimmune diseases treated with RTX, and those treated with other immunosuppressants, all of whom had been vaccinated with 2 doses of the mRNA COVID-19 vaccine.
METHODS
We performed anti-spike IgG and neutralization assays just before and 28 days after the second BNT162b2 (Pfizer-BioNTech) vaccine dose. The specific T cell response was assessed in activated CD4 and CD8 T cells using intracellular flow cytometry staining of cytokines (interferon-γ, tumor necrosis factor, and interleukin-2) after stimulation with SARS-CoV-2 spike peptide pools.
RESULTS
A lower proportion of responders with neutralizing antibodies to the vaccine was observed in the RTX group (29%; n = 24) compared to the other immunosuppressants group (80%; n = 35) (P = 0.0001) and the healthy control group (92%; n = 26) (P < 0.0001). No patients treated with RTX in the last 6 months showed a response. Time since last infusion was the main factor influencing humoral response in RTX-treated patients. The functional CD4 and CD8 cellular responses to SARS-CoV-2 peptides for each single cytokine or polyfunctionality were not different in the RTX group compared to the other immunosuppressants group or the control group. In RTX-treated patients, the T cell response was not different between patients with and those without a humoral response.
CONCLUSION
RTX induced a diminished antibody response to the mRNA COVID-19 vaccine, but the functional T cell response was not altered compared to healthy controls and autoimmune disease patients treated with other immunosuppressants. Further work is needed to assess the clinical protection granted by a functionally active T cell response in the absence of an anti-spike antibody response.
目的
已证明利妥昔单抗（RTX）治疗的患者对信使 RNA（mRNA）COVID-19 疫苗的抗体反应会减弱。我们进行这项研究是为了比较健康对照者、接受 RTX 治疗的自身免疫性疾病患者与接受其他免疫抑制剂治疗的患者之间的体液和 T 细胞反应，所有这些患者均已接种了 2 剂 mRNA COVID-19 疫苗。
方法
我们在接受第二剂 BNT162b2（辉瑞-生物科技）疫苗后 28 天之前和之后进行了抗尖峰 IgG 和中和抗体检测。通过使用细胞内流式细胞术染色刺激 SARS-CoV-2 尖峰肽库后的细胞因子（干扰素-γ、肿瘤坏死因子和白细胞介素-2）来评估活化的 CD4 和 CD8 T 细胞中的特异性 T 细胞反应。
结果
与其他免疫抑制剂组（80%，n=35）（P=0.0001）和健康对照组（92%，n=26）（P<0.0001）相比，RTX 组（29%，n=24）中疫苗中和抗体的应答者比例较低。在过去 6 个月内未接受 RTX 治疗的患者未显示出应答。接受 RTX 治疗的患者中，上次输注后时间是影响其体液反应的主要因素。与其他免疫抑制剂组或对照组相比，RTX 组中针对 SARS-CoV-2 肽的单个细胞因子或多功能性的功能性 CD4 和 CD8 细胞对 SARS-CoV-2 肽的反应没有差异。在接受 RTX 治疗的患者中，具有和不具有体液反应的患者之间的 T 细胞反应没有差异。
结论
RTX 诱导了对 mRNA COVID-19 疫苗的抗体反应减弱，但与健康对照者和接受其他免疫抑制剂治疗的自身免疫性疾病患者相比，功能性 T 细胞反应未改变。需要进一步的工作来评估在没有抗尖峰抗体反应的情况下，功能活跃的 T 细胞反应所提供的临床保护。
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