Hüper Sebastian, Eisele Florian, Duell Johannes, Schmalzing Marc, Nagler Lea, Strunz Patrick Pascal, Froehlich Matthias, Portegys Jan, Gernert Michael
Department of Internal Medicine II, Rheumatology/Clinical Immunology, University Hospital Würzburg, Oberdürrbacher Straße 6, 97080, Würzburg, Germany.
Practice for Rheumatology and Osteology, Bahnhofsplatz 5, 31134, Hildesheim, Germany.
BMC Rheumatol. 2025 Jul 9;9(1):84. doi: 10.1186/s41927-025-00542-7.
Janus kinase inhibitors (JAKi) represent a well-established therapeutic option for the treatment of autoimmune diseases. However, there is a paucity of evidence regarding their impact on de novo immune responses to vaccinations. T cells may confer long-lasting immunity and cross-recognise evolving epitopes of new viral variants, as evidenced by the SARS-CoV-2 vaccination. Consequently, we investigated the de novo T-cell response to SARS-CoV-2 vaccination in patients with rheumatic diseases undergoing treatment with JAK inhibitors.
Cross-sectional study, conducted in an outpatient department. Patients with rheumatic disease who had received two vaccinations against SARS-CoV-2 while under therapy with JAKi (n = 22) or tumour necrosis factor-blocking biologicals (TNFi) (control group n = 16) were recruited. To evaluate the vaccine-induced T cell response, the patients' PBMCs were stimulated with SARS-CoV-2 spike protein peptides. The percentage of CD4 T cells responding specifically to this stimulation by producing IFNγ was then measured using intracellular cytokine staining and flow cytometry. In addition antibody response to vaccination was assessed.
A specific T cell response was detected in 11 out of 22 (50.0%) of patients in the JAKi cohort, compared to 13 out of 16 (81.3%) of the TNFi cohort (p = 0.088). Patients on JAKi had a lower percentage of CD4 T cells responding to stimulation with SARS-CoV-2 spike peptides than patients on TNFi (p = 0.021). The proportion of patients with an antibody response and absolute anti-spike IgG levels did not significantly differ between the cohorts.
Patients on JAKi exhibited a compromised de novo T cell response to SARS-CoV-2 vaccination compared to TNFi patients. There is a need for further research on the effect of JAKi on T cell responses to vaccination.
Janus激酶抑制剂（JAKi）是治疗自身免疫性疾病的一种成熟的治疗选择。然而，关于它们对疫苗接种引发的从头免疫反应的影响，证据不足。T细胞可能赋予持久免疫力，并交叉识别新病毒变体不断演变的表位，如SARS-CoV-2疫苗接种所证明的那样。因此，我们研究了接受JAK抑制剂治疗的风湿性疾病患者对SARS-CoV-2疫苗接种的从头T细胞反应。
在门诊进行横断面研究。招募了在接受JAKi治疗（n = 22）或肿瘤坏死因子阻断生物制剂（TNFi）（对照组n = 16）期间接受过两次SARS-CoV-2疫苗接种的风湿性疾病患者。为了评估疫苗诱导的T细胞反应，用SARS-CoV-2刺突蛋白肽刺激患者的外周血单核细胞（PBMC）。然后使用细胞内细胞因子染色和流式细胞术测量通过产生IFNγ对这种刺激产生特异性反应的CD4 T细胞的百分比。此外，评估了对疫苗接种的抗体反应。
JAKi队列中的22名患者中有11名（50.0%）检测到特异性T细胞反应，而TNFi队列中的16名患者中有13名（81.3%）检测到特异性T细胞反应（p = 0.088）。与TNFi治疗的患者相比，接受JAKi治疗的患者对SARS-CoV-2刺突肽刺激产生反应的CD4 T细胞百分比更低（p = 0.021）。各队列之间有抗体反应的患者比例和抗刺突IgG绝对水平没有显著差异。
与TNFi患者相比，接受JAKi治疗的患者对SARS-CoV-2疫苗接种的从头T细胞反应受损。需要进一步研究JAKi对疫苗接种T细胞反应的影响。
