Responses to vaccination and to diseases vary widely across individuals, which may be partly due to baseline immune variations. Identifying such baseline predictors of immune responses and their biological basis is of broad interest, given their potential importance for cancer immunotherapy, disease outcomes, vaccination and infection responses. Here we uncover baseline blood transcriptional signatures predictive of antibody responses to both influenza and yellow fever vaccinations in healthy subjects. These same signatures evaluated at clinical quiescence are correlated with disease activity in patients with systemic lupus erythematosus with plasmablast-associated flares. CITE-seq profiling of 82 surface proteins and transcriptomes of 53,201 single cells from healthy high and low influenza vaccination responders revealed that our signatures reflect the extent of activation in a plasmacytoid dendritic cell–type I IFN–T/B lymphocyte network. Our findings raise the prospect that modulating such immune baseline states may improve vaccine responsiveness and mitigate undesirable autoimmune disease activity.

个体对疫苗接种和疾病的反应差异很大，这可能部分是由于基线免疫变化。鉴于它们对癌症免疫治疗、疾病结果、疫苗接种和感染反应的潜在重要性，确定此类免疫反应的基线预测因子及其生物学基础具有广泛的意义。在这里，我们发现了可预测健康受试者对流感和黄热病疫苗的抗体反应的基线血液转录特征。在临床静止期评估的这些相同特征与伴有浆母细胞相关耀斑的系统性红斑狼疮患者的疾病活动相关。82 种表面蛋白和 53 种转录组的 CITE-seq 分析，来自健康的高和低流感疫苗接种应答者的 201 个单细胞显示，我们的特征反映了浆细胞样树突状细胞 I 型 IFN-T/B 淋巴细胞网络的激活程度。我们的研究结果提出了这样的前景，即调节这种免疫基线状态可能会提高疫苗反应性并减轻不良的自身免疫性疾病活动。