Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France; Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France; Infection, Antimicrobiens, Modélisation, évolution (IAME), INSERM UMR 1137, Université Paris Cité, Paris, France.
Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France.
J Autoimmun. 2023 Jan;134:102987. doi: 10.1016/j.jaut.2022.102987. Epub 2022 Dec 19.
To evaluate the specific response of SLE patients to BNT162b2 vaccination and its impact on autoimmunity defined as in vivo production of interferon-alpha (IFNα) by plasmacytoid dendritic cells (pDCs) and autoreactive immune responses.
Our prospective study included SLE patients and healthy volunteers (HV) who received 2 doses of BNT162b2 vaccine 4 weeks apart. Subjects under immunosuppressive drugs or with evidence of prior COVID-19 were excluded. IgG anti-Spike SARS-CoV-2 (anti-S) antibodies, anti-S specific-B cells, anti-S specific T cells, in vivo INF-α production by pDCs, activation marker expression by pDCs and autoreactive anti-nuclear T cells were quantified before first injection, before second injection, and 3 and 6 months after first injection.
Vaccinated SLE patients produced significantly lower IgG antibodies and specific B cells against SARS-CoV-2 as compared to HV. In contrast, anti-S T cell response did not significantly differ between SLE patients and HV. Following vaccination, the surface expression of HLA-DR and CD86 and the in vivo production of IFNα by pDCs significantly increased in SLE patients. The boosted expression of HLA-DR on pDCs induced by BNT162b2 vaccine correlated with the overall immune responses against SARS-CoV-2 (anti-S antibodies: r = 0.27 [0.05-0.46], p = 0.02; anti-S B cells: r = 0.19 [-0.03-0.39], p = 0.09); anti-S T cells: r = 0.28 [0.05-0.47], p = 0.016). Eventually, anti-SARS-CoV-2 vaccination was associated with an overall decrease of autoreactive T cells (slope = - 0.00067, p = 0.015).
BNT162b2 vaccine induces a transient in vivo activation of pDCs in SLE that contributes to the immune responses against SARS-CoV-2. Unexpectedly BNT162b2 vaccine also dampens the pool of circulating autoreactive T cells, suggesting that vaccination may have a beneficial impact on SLE disease.
评估 SLE 患者对 BNT162b2 疫苗的特异性反应及其对自身免疫的影响，自身免疫定义为浆细胞样树突状细胞（pDC）体内产生干扰素-α（IFNα）和自身反应性免疫应答。
我们的前瞻性研究纳入了接受 2 剂 BNT162b2 疫苗（间隔 4 周）的 SLE 患者和健康志愿者（HV）。排除接受免疫抑制药物或有 COVID-19 既往史的患者。在第一次注射前、第二次注射前以及第一次注射后 3 个月和 6 个月，定量检测 IgG 抗尖峰 SARS-CoV-2（抗-S）抗体、抗-S 特异性 B 细胞、抗-S 特异性 T 细胞、pDC 体内 IFNα 产生、pDC 激活标志物表达和自身反应性抗核 T 细胞。
与 HV 相比，接种疫苗的 SLE 患者产生的 SARS-CoV-2 IgG 抗体和特异性 B 细胞明显较低。相反，SLE 患者和 HV 之间的抗-S 细胞反应无显著差异。接种后，SLE 患者 pDC 的 HLA-DR 和 CD86 表面表达以及 IFNα 的体内产生显著增加。BNT162b2 疫苗诱导的 pDC 上 HLA-DR 的增强表达与 SARS-CoV-2 的整体免疫反应相关（抗-S 抗体：r=0.27 [0.05-0.46]，p=0.02；抗-S B 细胞：r=0.19 [-0.03-0.39]，p=0.09）；抗-S T 细胞：r=0.28 [0.05-0.47]，p=0.016）。最终，抗 SARS-CoV-2 疫苗接种与自身反应性 T 细胞的整体减少相关（斜率=-0.00067，p=0.015）。
BNT162b2 疫苗在 SLE 中诱导 pDC 的体内瞬时激活，有助于 SARS-CoV-2 的免疫反应。出乎意料的是，BNT162b2 疫苗还抑制了循环自身反应性 T 细胞库，这表明疫苗接种可能对 SLE 疾病有有益的影响。
