Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus

Autor: Richard M. Siegel, Zerai Manna, William Rees, Adam Schiffenbauer, Wendy I. White, Michael A Smith, Sarfaraz Hasni, Chia-Chien Chiang, Katie Streicher, Kerry A. Casey, Frederick W. Miller, Dominic Sinibaldi, Kamelia Zerrouki, Saifur Rahman, Miguel A. Sanjuan, Mariana J. Kaplan, Lisa G. Rider
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-020-60563-9
Popis: Type I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Using a novel protocol we generated 1,132 aptamer-based protein measurements from anti-dsDNApos SLE blood samples and derived an IFN protein signature (IFNPS) that approximates the IFN 21-gene signature (IFNGS). Of 82 patients with SLE, IFNPS was elevated for 89% of IFNGS-high patients (49/55) and 26% of IFNGS-low patients (7/27). IFNGS-high/IFNPS-high patients exhibited activated NK, CD4, and CD8 T cells, while IFNPS-high only patients did not. IFNPS correlated with global disease activity in lymphopenic and non-lymphopenic patients and decreased following type I IFN neutralisation with anifrolumab in the SLE phase IIb study, MUSE. In summary, we developed a protein signature that reflects IFNGS and identifies a new subset of patients with SLE who have IFN activity.
Databáze: OpenAIRE
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