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

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Strauß R1, Rose T1, Flint SM2, Klotsche J3, Häupl T1, Peck-Radosavljevic M4, Yoshida T5, Kyogoku C6, Flechsig A1, Becker AM7, Dao KH7, Radbruch A3, Burmester GR1, Lyons PA2, Davis LS7, Hiepe F1, Grützkau A3, Biesen R8. J Mol Med (Berl). 2017 Jul;95(7):753-765. doi: 10.1007/s00109-017-1515-7. Epub 2017 Mar 29.

Abstract

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1 Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.

2 Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK.

3 German Rheumatism Research Center Berlin-Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.

4 Department of Gastroenterology and Hepatology, Medical University Vienna, 1090, Vienna, Austria.

5 Department of Pediatrics, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

6 Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

7 Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.

8 Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany. robert.biesen@charite.de.

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.