Immune mediators and metabolites to stratify SLE patients at high risk of cardio vascular diseases (IMSLE)

Concept

Accelerated atherosclerosis is an established complication of systemic autoimmune diseases, particularly SLE. Young female patients with SLE are more likely to develop myocardial infarction than matched healthy controls, and CVD is nowadays one of the most common causes of death (27%) in lupus patients. While traditional CV risk factors cannot explain such increased CV morbidity associated with SLE, common disease factors shared between SLE, atherosclerosis and treatment exposure may be of outmost importance in this process. Our group made 3 findings of particular interest that could link SLE pathogenesis and atherosclerosis-associated immune dysregulation: 1/ we identified specific immunometabolites (circulating nucleotide-derived metabolites), which are increased in the circulation of SLE patients. These immunometabolites trigger a constitutive inflammasome activation resulting in aberrant IL1-β production. Given that IL1-β inhibition was reported to significantly reduce CV events without altering lipid levels, we propose that these immunometabolites may represent novel candidate biomarkers of CV risk stratification in SLE. 2/ we identified OX40L as an important costimulatory molecule implicated in follicular helper T cell (Tfh) activation in SLE. Interestingly, OX40L polymorphism has been associated to both SLE and atherosclerosis, and Tfh have been recently shown to accelerate atherosclerosis progression. 3/ Immune complexes-activated platelets sustain aberrant immune response in SLE and block immunosuppressive functions of regulatory T cells (Tregs). Selectins and Tregs cell dysfunction are well accepted players in atherosclerosis pathogenesis. Thus there are multiple pathways that are shared between SLE and atherosclerosis and that may results in an increased risk of CV-associated morbidity in SLE patients. Exploring these interconnected pathways in SLE patients together with traditional and other well-established disease-related factors, might lead to a better stratification of CV risk in SLE.

Facts and figures

Project lead
P Duffau
CHU of Bordeaux
pierre.duffau@chu-bordeaux.fr
patrick.blanco@chu-bordeaux.fr
FOREUM research grant: €595'000
2019–2022

Meet the team

P Duffau
CHU of Bordeaux
pierre.duffau@chu-bordeaux.fr
P Blanco
University Hospital Bordeaux
B Faustin
University Hospital Bordeaux
C Richez
University Hospital Bordeaux
T Martin
University Hospital Strasbourg
G Ruiz-Irastorza
Hospital Universitario Cruces
R Voll
Albert Ludwig University Freiburg

Objectives

The general objective of this study is to investigate the accuracy, predictive value and utility of immunological disease-related biomarkers in stratifying CV risk in patients with SLE.

Patient voice

Patients had already participated in the grant preparation phase, helping the research team to identify and prioritize key research topics and objectives. Then, they helped us in the study protocol elaboration especially to provide complementary views on ethical considerations that are inherent to certain aspects of the research plan.

We would like to include them in the data analysis to improve the ability of the research team to design a more focused analysis and to contextualize conclusions.