Nat. Med. https://doi.org/10.1038/s41591-020-0769-8 (2020)

Individual responses to vaccination can vary widely, making it difficult to predict whether someone will mount a robust antibody response or a poor response. In Nature Medicine, Tsang and colleagues identify a prevaccination blood transcriptional signature (TGSig) that can predict ‘high’ and ‘low’ responders. TGSig is stably expressed at baseline in healthy individuals. Interestingly, for a subset of patients with systemic lupus erythematosus (SLE), whose disease is correlated with plasmablast frequency, this same TGSig expressed during periods of disease quiescence is predictive of flare intensity. Single-cell CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) analysis revealed that plasmacytoid dendritic cells, rather than B cells, are primarily responsible for the differences observed in gene expression that define the blood TGSig. Accordingly, type I interferon expression by plasmacytoid dendritic cells is linked to elevated activation of B and T cells, consistent with the higher immune response seen in healthy individuals and the more severe flares in the SLE cohort.