Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell, Manhasset, New York, USA.
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
JCI Insight. 2024 Jun 4;9(13):e180750. doi: 10.1172/jci.insight.180750.
Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 patients with autoimmune diseases, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti-spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell-depleted patients with multiple sclerosis (MS) were associated with higher CD8 T cell responses. By contrast, patients taking mycophenolate mofetil (MMF) exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low anti-spike IgG response included B cell depletion within the last year, fingolimod, and combination treatment with MMF and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of preexisting anti-type I IFN antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2-related deaths suggest that T cell immunity contributes to protection in autoimmune disease.
患有自身免疫性疾病的患者由于其基础疾病和免疫抑制治疗,发生严重感染的风险更高。在这项对 463 名自身免疫性疾病患者的真实世界观察性研究中,我们研究了 SARS-CoV-2 疫苗接种后 B 和 T 细胞反应不良的危险因素。我们发现,自身免疫人群中疫苗接种和加强针后抗刺突 IgG 反应不足的频率很高,但 T 细胞反应抑制最小。多发性硬化症(MS)患者的 B 细胞耗竭后 IgG 反应较低与更高的 CD8 T 细胞反应相关。相比之下,服用吗替麦考酚酯(MMF)的患者 B 和 T 细胞反应受到一致抑制。与低抗刺突 IgG 反应相关的治疗风险最高的治疗方法包括过去一年内 B 细胞耗竭、芬戈莫德以及 MMF 和贝利尤单抗联合治疗。我们的数据表明,mRNA-1273(Moderna)疫苗是自身免疫人群中最有效的疫苗。接种疫苗后,无论是疾病发作还是自身抗体均很少诱导,预先存在的抗 I 型干扰素抗体对疫苗反应或突破性感染均无显著影响。突破性感染的低频率和缺乏与 SARS-CoV-2 相关的死亡表明 T 细胞免疫有助于自身免疫性疾病的保护。