Université de Paris, Service de Rhumatologie.
Université de Paris, Service de Virologie, Hôpital Cochin, AP-HP.CUP, Paris, France.
Rheumatology (Oxford). 2022 Jun 28;61(SI2):SI163-SI168. doi: 10.1093/rheumatology/keab815.
To identify which factors influence humoral response to coronavirus disease 2019 (COVID-19) vaccination in rituximab (RTX)-treated patients.
This was an observational, prospective, usual care study including consecutive patients with inflammatory rheumatic diseases in maintenance therapy with RTX. All patients received a two-dose regimen COVID-19 vaccination. Serum IgG antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins were measured at the time of the new RTX infusion.
From the recruited patients, 16/45 (36%) produced antibodies reaching the assay cut-off value of 15 AU/ml and 29/45 (64%) had a negative serology. Within RTX-treated patients, 25 (56%) had undetectable B cells. Negative serology was associated with undetectable B cells (24/25 vs 5/20, P < 0.001). Moreover, SARS-CoV-2 spike antibodies correlated with CD19 counts (r = 0.86, P < 0.001). The effect of RTX and MTX was additive in terms of seroconversion rates (23% vs 50% in patients receiving RTX in monotherapy, P = 0.12) and SARS-CoV-2 spike antibody levels [3.80 (95% CI 3.80, 7.50) vs 75 (95% CI 3.8, 353) AU/ml in patients receiving RTX in monotherapy; P = 0.025]. Multivariate analyses including demographics, disease characteristics, gammaglobulin levels, RTX and other therapies used, CD19 counts, and the time between the last RTX infusion and vaccination identified detectable B cells as the only variable independently associated with seropositivity [odds ratio 35.2 (95% CI 3.59, 344.20)].
B cell depletion is the main independent contributing factor of antibody response to SARS-CoV-2 vaccination in RTX-treated patients. Monitoring CD19 may be of interest to identify the most appropriate period to perform vaccination.
确定影响利妥昔单抗（RTX）治疗患者对 2019 年冠状病毒病（COVID-19）疫苗产生体液免疫反应的因素。
这是一项观察性、前瞻性、常规护理研究，纳入了正在接受 RTX 维持治疗的炎症性风湿病患者。所有患者均接受了两剂 COVID-19 疫苗接种。在新的 RTX 输注时，测量针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突蛋白的血清 IgG 抗体水平。
在招募的患者中，16/45（36%）产生了达到 15 AU/ml 检测截止值的抗体，29/45（64%）血清学检测为阴性。在 RTX 治疗的患者中，25 例（56%）存在无法检测到的 B 细胞。阴性血清学与无法检测到的 B 细胞相关（24/25 例 vs 5/20 例，P < 0.001）。此外，SARS-CoV-2 刺突抗体与 CD19 计数相关（r = 0.86，P < 0.001）。RTX 和 MTX 在血清转化率方面具有相加作用（接受 RTX 单药治疗的患者为 23%，接受 RTX 联合 MTX 治疗的患者为 50%，P = 0.12）和 SARS-CoV-2 刺突抗体水平[接受 RTX 单药治疗的患者为 3.80（95%CI 3.80，7.50），接受 RTX 联合 MTX 治疗的患者为 75（95%CI 3.8，353）AU/ml；P = 0.025]。包括人口统计学、疾病特征、丙种球蛋白水平、RTX 和其他使用的治疗药物、CD19 计数以及最后一次 RTX 输注和疫苗接种之间的时间在内的多变量分析确定，可检测到的 B 细胞是与血清阳性独立相关的唯一变量[优势比 35.2（95%CI 3.59，344.20）]。
B 细胞耗竭是 RTX 治疗患者对 SARS-CoV-2 疫苗产生体液免疫反应的主要独立影响因素。监测 CD19 可能有助于确定进行疫苗接种的最佳时间。
