An Zesheng, Zhou Xian, Li Yanfeng, Jaquith Jane, McCarthy-Fruin Kathleen, Sletten Jennifer, Warrington Kenneth J, Weyand Cornelia, Crowson Cynthia S, Chumsri Saranya, Knutson Keith L, Figueroa-Parra Gabriel, Sanchez-Rodriguez Alain, Thanarajasingam Uma, Duarte-García Alí, Zeng Hu
Division of Rheumatology, Department of Medicine, Mayo Clinic Rochester, MN 55905, USA.
Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, P. R. China, 300211.
medRxiv. 2023 Mar 27:2023.03.22.23287597. doi: 10.1101/2023.03.22.23287597.
To evaluate seroreactivity and disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases.
We collected biological samples longitudinally before and after 2-3 doses of COVID-19 mRNA vaccines from a cohort of patients with systemic lupus erythematosus (SLE), psoriatic arthritis, Sjogren's syndrome, ankylosing spondylitis, and inflammatory myositis. Anti-SARS-CoV-2 spike IgG and IgA and anti-dsDNA concentration were measured by ELISA. A surrogate neutralization assay was utilized to measure antibody neutralization ability. Lupus disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Expression of type I interferon signature was measured by real-time PCR. The frequency of extrafollicular double negative 2 (DN2) B cells was measured by flow cytometry.
Most of the patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Rituximab treatment substantially reduced antibody level and neutralization ability. Among SLE patients, no consistent increase in SLEDAI scores was observed post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I IFN signature genes were highly variable but did not show consistent or significant increases. Frequency of DN2 B cells remained largely stable.
Rheumatic disease patients without rituximab treatment have robust antibody responses toward COVID-19 mRNA vaccination. Disease activity and disease-associated biomarkers remain largely stable over 3 doses of vaccines, suggesting that COVID-19 mRNA vaccines may not exacerbate rheumatic diseases.
Patients with rheumatic diseases mount robust humoral immunity towards 3 doses of COVID-19 mRNA vaccines.Disease activity and biomarkers remain stable following 3 doses of COVID-19 mRNA vaccines.
评估2剂或3剂新型冠状病毒肺炎（COVID-19）mRNA疫苗接种后，一组风湿性疾病患者的血清反应性和疾病生物标志物。
我们从一组系统性红斑狼疮（SLE）、银屑病关节炎、干燥综合征、强直性脊柱炎和炎性肌病患者中，在接种2 - 3剂COVID-19 mRNA疫苗前后纵向收集生物样本。采用酶联免疫吸附测定（ELISA）法检测抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白IgG和IgA以及抗双链DNA（dsDNA）浓度。利用替代中和试验检测抗体中和能力。采用系统性红斑狼疮疾病活动指数（SLEDAI）评估狼疮疾病活动度。通过实时聚合酶链反应（PCR）检测I型干扰素特征的表达。采用流式细胞术检测滤泡外双阴性2（DN2）B细胞的频率。
大多数患者在接种2剂mRNA疫苗后产生了与健康对照相当的高SARS-CoV-2刺突蛋白特异性中和抗体。抗体水平随时间下降，但在接种第三剂疫苗后恢复。利妥昔单抗治疗显著降低了抗体水平和中和能力。在SLE患者中，接种疫苗后未观察到SLEDAI评分持续升高。抗dsDNA抗体浓度和I型干扰素特征基因表达的变化高度可变，但未显示出持续或显著增加。DN2 B细胞频率基本保持稳定。
未接受利妥昔单抗治疗的风湿性疾病患者对COVID-19 mRNA疫苗有较强的抗体反应。在接种3剂疫苗过程中，疾病活动度和疾病相关生物标志物基本保持稳定，提示COVID-19 mRNA疫苗可能不会加重风湿性疾病。
风湿性疾病患者对3剂COVID-19 mRNA疫苗产生较强的体液免疫。接种3剂COVID-19 mRNA疫苗后疾病活动度和生物标志物保持稳定。
