Background In SLE, heterogeneous clinical expression and activity may reflect diverse pathogenic and/or effector mechanisms. We dwelled into SLE heterogeneity by assessing the expression of three gene sets representative of type I interferon (IFN-I), neutrophil-(PMN) and plasmablast-(PB) signatures in a well characterized, multidisciplinary cohort of SLE patients. We further assessed whether individual gene products could be representative of these three signatures.
Methods Whole blood, serum and clinical data were obtained from 140 SLE individuals. Gene expression was assessed by NanoString© technology, using a panel of 37 probes allowing the computation of six IFN-I, one PMN and one PB scores. Protein levels were measured by ELISA.
Results High IFN-I gene expression was found in 45 to 50% of SLE individuals, depending on the score used. All 6 IFN-I scores were significantly associated with active skin involvement and 2 of 6 with arthritis. Interferon-induced GTP-binding protein Mx1 (MX1) correlated with IFN-I score (p<0.0001) and was associated with a similar clinical phenotype. High PMN gene expression was found in 25% of individuals in association with SLE fever, serositis, leukopenia and glucocorticoid use. PB gene expression was highly influenced by immunosuppressant agents with no association with SLE features. The combined IFN-I and PMN gene expression was significantly associated with high disease activity and outperformed anti-dsDNA, anti C1q and complement levels to predict SLE activity.
Conclusions The IFN-I and PMN gene scores segregate with distinct SLE clinical features and their joint expression identify high disease activity. MX1 protein levels perform similarly to IFN-I gene expression.
Acknowledgements Work partially supported by funds provided by a grant from Fondation Fleurette Wagemakers, Sion (Switzerland), by a grant from La Société Académique de Genève (Switzerland). FC was supported by a research travel grant from the French Society of Dermatology and from Institut Servier, Paris (France).
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.