Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Paris, France.
Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière (GHPS), French National Reference Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Sorbonne Université, Paris, France.
Ann Rheum Dis. 2022 Apr;81(4):575-583. doi: 10.1136/annrheumdis-2021-221097. Epub 2021 Oct 4.
Our aim was to evaluate systemic lupus erythematosus (SLE) disease activity and SARS-CoV-2-specific immune responses after BNT162b2 vaccination.
In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine until day 15 after the second dose in 126 patients with SLE. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T cell responses were quantified by interferon-γ release assay after the second dose.
BNT162b2 was well tolerated and no statistically significant variations of BILAG (British Isles Lupus Assessment Group) and SLEDAI (SLE Disease Activity Index) scores were observed throughout the study in patients with SLE with active and inactive disease at baseline. Mycophenolate mofetil (MMF) and methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody response (β=-78, p=0.007; β=-122, p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total immunoglobulin G serum levels, naïve B cell frequencies (β=2, p=0.018; β=2.5, p=0.003) and SARS-CoV-2-specific T cell response (r=0.462, p=0.003). In responders, serum neutralisation activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients.
MMF, MTX and poor baseline humoral immune status, particularly low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating patients with SLE who might need adapted vaccine regimens and follow-up.
评估系统性红斑狼疮（SLE）患者接种 BNT162b2 疫苗后的疾病活动度和 SARS-CoV-2 特异性免疫反应。
在这项前瞻性研究中，我们对 126 例 SLE 患者从第一剂疫苗开始直至第二剂疫苗后第 15 天进行疾病活动度和临床评估。我们测量了针对野生型刺突抗原的 SARS-CoV-2 抗体反应，同时评估了针对 SARS-CoV-2 历史株和关注变异株（VOCs）的血清中和活性。在接种第二剂疫苗后，通过干扰素-γ释放试验定量检测疫苗特异性 T 细胞反应。
BNT162b2 疫苗耐受性良好，在基线时患有活动性和非活动性疾病的 SLE 患者中，整个研究期间 BILAG（不列颠群岛狼疮评估组）和 SLEDAI（SLE 疾病活动指数）评分均无统计学显著变化。霉酚酸酯（MMF）和甲氨蝶呤（MTX）治疗与 BNT162b2 抗体反应明显降低相关（β=-78，p=0.007；β=-122，p<0.001）。抗刺突抗体反应与基线总免疫球蛋白 G 血清水平、幼稚 B 细胞频率（β=2，p=0.018；β=2.5，p=0.003）和 SARS-CoV-2 特异性 T 细胞反应呈正相关（r=0.462，p=0.003）。在应答者中，针对携带 E484K 突变的 VOCs 的血清中和活性降低，但在大多数患者中仍可检测到。
MMF、MTX 和较差的基线体液免疫状态，特别是低幼稚 B 细胞频率，与 BNT162b2 mRNA 抗体反应受损独立相关，确定了 SLE 患者可能需要适应性疫苗方案和随访。
