Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus

• Published in: Nature medicine Vol. 26; no. 4; pp. 618 - 629
• Main Authors: Kotliarov, Yuri, Sparks, Rachel, Martins, Andrew J., Mulè, Matthew P., Lu, Yong, Goswami, Meghali, Kardava, Lela, Banchereau, Romain, Pascual, Virginia, Biancotto, Angélique, Chen, Jinguo, Schwartzberg, Pamela L., Bansal, Neha, Liu, Candace C., Cheung, Foo, Moir, Susan, Tsang, John S.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2020; Nature Publishing Group
• Subjects: 631/114/2413; 631/250/254; 631/250/590; 692/53/2423; 692/699/249/1313/1613; Adaptive Immunity - genetics; Adolescent; Adult; Aged; Aged, 80 and over; Analysis; Antibodies; Antibody Formation - genetics; Autoimmune diseases; B-Lymphocytes; Biomedical and Life Sciences; Biomedicine; Cancer immunotherapy; Cancer Research; Care and treatment; Cell activation; Child; Child, Preschool; Chronic conditions; Circuits; Cohort Studies; Dendritic cells; Disease; Disease control; Female; Flares; Gene expression; Gene Expression Profiling; Health risk assessment; Humans; Immune response; Immunotherapy; Infectious Diseases; Influenza; Influenza vaccines; Influenza Vaccines - immunology; Influenza, Human - prevention & control; Interferon; Lupus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Lymphocytes; Lymphocytes B; Male; Metabolic Diseases; Middle Aged; Molecular Medicine; Neurosciences; Patient outcomes; Prevention; Proteins; Signatures; Single-cell protein; Systemic lupus erythematosus; Transcription; Transcriptome - immunology; Vaccination; Vaccines; Vector-borne diseases; Yellow fever; Yellow Fever - prevention & control; Yellow Fever Vaccine - immunology; Young Adult; United States
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-020-0769-8

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. Simultaneous single-cell protein and transcriptome analysis identifies a baseline immune circuit associated with antibody responses to vaccination in healthy individuals and the severity of disease flares in patients with a subtype of systemic lupus erythematosus.