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.
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.
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The work was supported by the Sixth Framework Programme (project AutoCure; LSHB-CT-2006-018861), the German Research Foundation (grant number SFB650 TP12), the IMI JU-funded project BeTheCure (contract number 115142-29), and the Zukunftsfond Berlin (contract number 101399339). PAL and SMF were funded by project grants from the Medical Research Council (G0400929) and the Wellcome Trust (094227/Z/10/Z). SMF was supported by a Wellcome Trust Translational Medicine and Therapeutics PhD Studentship. Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (079895). LSD was supported by an Alliance for Lupus Research (ALR) Award #257549 and National Institutes of Health grants AR067625 (PI, Satterthwaite) and AI122720 (PI, Satterthwaite).
Conflict of interest
The authors declare that they have no conflict of interest.
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Strauß, R., Rose, T., Flint, S.M. et al. Type I interferon as a biomarker in autoimmunity and viral infection: a leukocyte subset-specific analysis unveils hidden diagnostic options. J Mol Med 95, 753–765 (2017). https://doi.org/10.1007/s00109-017-1515-7