Are interferon-related biomarkers advantageous for monitoring disease activity in systemic lupus erythematosus? A longitudinal benchmark study

Thomas Rose, Andreas Grützkau, Jens Klotsche, Philipp Enghard, Alexandra Flechsig, Johannes Keller, Gabriela Riemekasten, Andreas Radbruch, Gerd Rüdiger Burmester, Thomas Dörner, Falk Hiepe*, Robert Biesen

*Korrespondierende/r Autor/-in für diese Arbeit
19 Zitate (Scopus)

Abstract

Objective. To determine the clinical value of six traditional and three IFN-related biomarkers in monitoring disease activity (DA) in SLE. Methods. Prospective longitudinal study of IFNα, IFNγ-inducible protein 10 (IP-10) and sialic acid-binding Iglike lectin 1 (SIGLEC1) vs antibodies against dsDNA (ELISA and Farr radioimmunoassay), dsDNA-complexed nucleosomes (anti-dsDNA-NcX: ELISA), nucleosomes (ANuA: ELISA) and complement C3/C4 for correlation with DA (measured by BILAG 2004 index) in 26 SLE patients (77 visits). Optimal upper and lower longitudinal thresholds for the biomarkers and their accuracies for reflecting clinically relevant changes in DA (flares and remission) were determined by receiver operating characteristic and Youden index analysis. Results. Increases in IP-10, SIGLEC1 and ANuA to + 101.6 pg/ml, +5.01 relative mean fluorescence intensity and +16.20 IU/ml above the calculated upper longitudinal threshold significantly reflected lupus flares, with a sensitivity and specificity of 50 and 95% for IP-10, 83 and 90% for SIGLEC1 and 58 and 95% for ANuA. Decreases in anti-dsDNA (ELISA), IFNα and anti-dsDNA (Farr assay) to -64.7 IU/ml, -16.69 pg/ml and -3.3 IU/ml below lower longitudinal thresholds, respectively, best reflected remission, with sensitivity and specificity of 75 and 95%, 62 and 90%, and 75 and 90%, respectively. Conclusion. IP-10, SIGLEC1 and ANuA emerged as advantageous biomarkers for monitoring disease activity. This is the first study in SLE that provides longitudinal biomarker thresholds and test accuracies for SLE flares and remitting disease. In the context of IFN-directed therapies, chemokines and fluorescence- activated cell sorting-based IFN biomarkers for monitoring SLE activity should be further studied.

OriginalspracheEnglisch
ZeitschriftRheumatology (United Kingdom)
Jahrgang56
Ausgabenummer9
Seiten (von - bis)1618-1626
Seitenumfang9
ISSN1462-0324
DOIs
PublikationsstatusVeröffentlicht - 01.09.2017

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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