Trinity Kidney Centre, Trinity Translational Medicine Institute, School of Medicine, Trinity College Dublin, D08 W9RT Dublin, Ireland.
Department of Nephrology, Galway University Hospital, H91 YR71 Galway, Ireland.
Int J Mol Sci. 2024 May 11;25(10):5239. doi: 10.3390/ijms25105239.
Immunosuppressive treatment in patients with rheumatic diseases can maintain disease remission but also increase risk of infection. Their response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is frequently blunted. In this study we evaluated the effect of immunosuppression exposure on humoral and T cell immune responses to SARS-CoV-2 infection and vaccination in two distinct cohorts of patients; one during acute SARS-CoV-2 infection and 3 months later during convalescence, and another prior to SARS-CoV-2 vaccination, with follow up sampling 6 weeks after vaccination. Results were compared between rituximab-exposed (in previous 6 months), immunosuppression-exposed (in previous 3 months), and non-immunosuppressed groups. The immune cell phenotype was defined by flow cytometry and ELISA. Antigen specific T cell responses were estimated using a whole blood stimulation interferon-γ release assay. A focused post-vaccine assessment of rituximab-treated patients using high dimensional spectral cytometry was conducted. Acute SARS-CoV-2 infection was characterised by T cell lymphopenia, and a reduction in NK cells and naïve CD4 and CD8 cells, without any significant differences between immunosuppressed and non-immunosuppressed patient groups. Conversely, activated CD4 and CD8 cell counts increased in non-immunosuppressed patients with acute SARS-CoV-2 infection but this response was blunted in the presence of immunosuppression. In rituximab-treated patients, antigen-specific T cell responses were preserved in SARS-CoV-2 vaccination, but patients were unable to mount an appropriate humoral response.
在风湿性疾病患者中,免疫抑制治疗可以维持疾病缓解,但也会增加感染的风险。他们对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)疫苗的反应常常受到抑制。在这项研究中,我们评估了免疫抑制暴露对两种不同患者队列中 SARS-CoV-2 感染和疫苗接种后体液和 T 细胞免疫反应的影响;一组在急性 SARS-CoV-2 感染期间,另一组在感染后 3 个月的恢复期,另一组在 SARS-CoV-2 疫苗接种前进行,并在接种后 6 周进行随访采样。比较了利妥昔单抗暴露(前 6 个月)、免疫抑制暴露(前 3 个月)和非免疫抑制组之间的结果。通过流式细胞术和 ELISA 定义免疫细胞表型。使用全血刺激干扰素-γ释放测定法估计抗原特异性 T 细胞反应。对接受利妥昔单抗治疗的患者进行了高维光谱细胞术的疫苗接种后重点评估。急性 SARS-CoV-2 感染的特点是 T 细胞淋巴细胞减少,NK 细胞和幼稚 CD4 和 CD8 细胞减少,但免疫抑制和非免疫抑制患者组之间没有明显差异。相反,非免疫抑制患者急性 SARS-CoV-2 感染后 CD4 和 CD8 细胞的激活计数增加,但在免疫抑制存在的情况下,这种反应受到抑制。在接受利妥昔单抗治疗的患者中,SARS-CoV-2 疫苗接种中保留了抗原特异性 T 细胞反应,但患者无法产生适当的体液反应。