Immunology Outpatient Clinic, Vienna, Austria.
Department for Biomedical Research, Center of Experimental Medicine, Danube University Krems, Krems an der Donau, Austria.
Front Immunol. 2022 Feb 14;13:827048. doi: 10.3389/fimmu.2022.827048. eCollection 2022.
Previous studies on immune responses following COVID-19 vaccination in patients with common variable immunodeficiency (CVID) were inconclusive with respect to the ability of the patients to produce vaccine-specific IgG antibodies, while patients with milder forms of primary antibody deficiency such as immunoglobulin isotype deficiency or selective antibody deficiency have not been studied at all. In this study we examined antigen-specific activation of CXCR5-positive and CXCR5-negative CD4 memory cells and also isotype-specific and functional antibody responses in patients with CVID as compared to other milder forms of primary antibody deficiency and healthy controls six weeks after the second dose of BNT162b2 vaccine against SARS-CoV-2. Expression of the activation markers CD25 and CD134 was examined by multi-color flow cytometry on CD4 T cell subsets stimulated with SARS-CoV-2 spike peptides, while in parallel IgG and IgA antibodies and surrogate virus neutralization antibodies against SARS-CoV-2 spike protein were measured by ELISA. The results show that in CVID and patients with other milder forms of antibody deficiency normal IgG responses (titers of spike protein-specific IgG three times the detection limit or more) were associated with intact vaccine-specific activation of CXCR5-negative CD4 memory T cells, despite defective activation of circulating T follicular helper cells. In contrast, CVID IgG nonresponders showed defective vaccine-specific and superantigen-induced activation of both CD4T cell subsets. In conclusion, impaired TCR-mediated activation of CXCR5-negative CD4 memory T cells following stimulation with vaccine antigen or superantigen identifies patients with primary antibody deficiency and impaired IgG responses after BNT162b2 vaccination.
先前关于 COVID-19 疫苗接种后在普通变异性免疫缺陷（CVID）患者中免疫反应的研究对于患者产生疫苗特异性 IgG 抗体的能力尚无定论，而对于较轻形式的原发性抗体缺陷（如免疫球蛋白同种型缺陷或选择性抗体缺陷）的患者则根本没有研究过。在这项研究中，我们检查了 CVID 患者与其他较轻形式的原发性抗体缺陷患者和健康对照组在接受第二剂 BNT162b2 疫苗接种后 6 周后，抗原特异性激活 CXCR5 阳性和 CXCR5 阴性 CD4 记忆细胞，以及同种型特异性和功能性抗体反应。通过多色流式细胞术检查用 SARS-CoV-2 刺突肽刺激的 CD4 T 细胞亚群上的激活标志物 CD25 和 CD134 的表达，同时通过 ELISA 平行测量 IgG 和 IgA 抗体以及针对 SARS-CoV-2 刺突蛋白的替代病毒中和抗体。结果表明，在 CVID 和其他较轻形式的抗体缺陷患者中，正常的 IgG 反应（刺突蛋白特异性 IgG 滴度是检测限的三倍或更高）与 CXCR5 阴性 CD4 记忆 T 细胞的完整疫苗特异性激活相关，尽管循环滤泡辅助 T 细胞的激活受损。相比之下，CVID IgG 无应答者显示出疫苗特异性和超抗原诱导的两种 CD4T 细胞亚群的激活缺陷。总之，疫苗抗原或超抗原刺激后 CXCR5 阴性 CD4 记忆 T 细胞的 TCR 介导的激活受损可识别原发性抗体缺陷和 BNT162b2 接种后 IgG 反应受损的患者。
