Background Over the decades, IFNα has been identified as a key cytokine predisposing and driving systemic lupus erythematosus pathology and is thus a frequently studied target molecule. It is assumed that IFNα can serve both as a biomarker of disease activity and as a companion diagnostic test for IFN inhibitors. IP-10 and Siglec-1, both response proteins of IFNα, have previously been shown to be suitable biomarkers for disease activity in SLE. A sensitive and reliable detection method for IFNα is indispensable, however a standard has yet to be established.
Objectives Evaluation and comparison of clinical efficacy of three biomarkers for interferon activity (measured directly and indirectly) and six traditional biomarkers to indicate current and prospective disease activity in SLE.
Methods IFNα (DELFIA), IP-10 (ELISA) and Siglec-1 expression on monocytes was measured by flow cytometry in 79 accurately characterized lupus patients and compared to serum titres of Anti-dsDNA (ELISA and RIA), Anti-dsDNA-NcX ELISA, Anti-Nuc ELISA, C3 and C4. 31 clinically quiescent patients were monitored for flares over the course of 180 days. Disease activity was evaluated using BILAG-2004.
Results Increased IFN biomarkers were found for IFNα in 53%, IP-10 in 47% and Siglec-1 in 79% of this lupus cohort. IFNα (r=0.45; p<0.0001) and Siglec-1 (r=0.54; p<0.0001) correlated better with BILAG-2004 than IP-10 (r=0.38; p=0.0002), Farr assay (r=0.40; p=0.0001), Anti-dsDNA-NcX ELISA (r=0.28; p=0.0061), Anti-dsDNA ELISA (r=0.31; p=0.0025), Anti-Nuc ELISA (r=0.25; p=0.0121), C3 (r=-0.43; p<0.0001) and C4 (r=-0.33; p=0.0013). The best predictors of SLE flares were low lymphocyte count, short disease duration, mild clinical activity, low complement C3 and high IFNα.
Conclusions IFNα and Siglec-1 expression on monocytes emerged as the best biomarkers of disease activity in lupus patients.
Therefore, implementation of IFN biomarkers in standard lupus diagnostics should be reappraised, especially in view of new and emerging anti-IFN-directed therapies.
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Disclosure of Interest None Declared
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