Type I interferon as a biomarker in autoimmunity and viral infection: a leukocyte subset-specific analysis unveils hidden diagnostic options

Romy Strauß, Thomas Rose, Shaun M. Flint, Jens Klotsche, Thomas Häupl, Markus Peck-Radosavljevic, Taketoshi Yoshida, Chieko Kyogoku, Alexandra Flechsig, Amy M. Becker, Kathryn H. Dao, Andreas Radbruch, Gerd Rüdiger Burmester, Paul A. Lyons, Laurie S. Davis, Falk Hiepe, Andreas Grützkau, Robert Biesen

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Abstract: Interferon alpha and its surrogates, including IP-10 and SIGLEC1, paralleled changes of disease activity in systemic lupus erythematosus (SLE). However, the whole blood interferon signature (WBIFNS)—the current standard for type I IFN assessment in SLE—does not correlate with SLE disease activity in individual patients over time. The underlying causes for this apparent contradiction have not been convincingly demonstrated. Using a multicenter dataset of gene expression data from leukocyte subsets in SLE, we identify distinctive subset-specific contributions to the WBIFNS. In a subsequent analysis, the effects of type I interferon on cellular blood composition in patients with SLE and hepatitis B were also studied over time. We found that type I interferon mediates significant alterations in whole blood composition, including a neutropenia and relative lymphocytosis. Given different effects of type 1 interferon on different leukocyte subsets, these shifts confound measurement of a type 1 interferon signature in whole blood. To minimize and overcome these limitations of the WBIFNS, we suggest to measure IFN-induced transcripts or proteins in a specific leukocyte subset to improve clinical impact of interferon biomarkers. Key messages: Myeloid cells contribute more to the WBIFNS in SLE than their lymphocytic counterpart.Very similar leukocyte subsets reveal distinctive IFN signatures.IFN alpha mixes up composition of blood and leads to a preferential neutropenia, yielding relative lymphocytosis.

Original languageEnglish (US)
Pages (from-to)753-765
Number of pages13
JournalJournal of Molecular Medicine
Volume95
Issue number7
DOIs
StatePublished - Jul 1 2017

Keywords

  • Biomarker
  • Disease activity
  • Systemic lupus erythematosus
  • Type I interferon

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Type I interferon as a biomarker in autoimmunity and viral infection: a leukocyte subset-specific analysis unveils hidden diagnostic options'. Together they form a unique fingerprint.

Cite this