Deciphering the role of Reactive Oxygen Species and Neutrophils in the SLE pathogenesis

Objectives of the Project

We have previously seen that reduced ability of neutrophils to produce reactive oxygen species (ROS) is associated with increased severity and organ damage in SLE. This prompted us to ask if SLE patients are genetically predisposed to have low ROS production and how this would influence pathogenesis. We are investigating the role of NCF1 gene variants in SLE and relate this to disease phenotypes. We are also characterizing the role of ROS and neutrophils in regulation of key immunopathogenic events in SLE, focusing on NETosis, type I interferon production and activation of adaptive immunity.

Facts and Figures

Project Lead
Prof. A. Bengtsson
Lund University
FOREUM research grant: € 150.000
March 2016, Duration 3 years

Meet the Team

Prof. A. Bengtsson
Lund University
Prof. A. Blom
Lund University
Prof. N. Heegard
Statens Serum Institut
Prof. M. Herrmann
Friedrich-Alexander University Erlangen - Nuremberg
Prof. R. Holmdahl
Karolinska Institutet
Prof. F. Ivars
Lund University
Prof. S. Jacobsen
Copenhagen University

Patient Voice

We are since many years always working in close collaboration with patients that are also taking part in the projects, letting us be influenced by patients from their perspectives.

Interim Results

This investigation aims at identifying novel ROS-related immunopathological events in SLE to provide new therapeutic targets and to develop clinical tools to monitor and predict disease activity and severity and thus prevent organ damage and premature mortality. We have identified an association of a SNP in NCF1 with Swedish SLE patients. The frequency of the associated T-allele is 11% in patients compared to 4% in controls, odds ratio 3.0, P-value 7x10-20. We have also found that the associated T-allele reduces ROS production in neutrophils from SLE patients  and leads to a younger diagnosis age.

Publications

Olsson LM et al. A SNP in the gene NCF1 leading to a reduced oxidative burst is associated with SLE. http://dx.doi.org/10.1136/annrheumdis-2017-211287. [Epub ahead of print]. Link