Immune Mediators and Metabolites to Stratify Systemic Lupus Erythematosus Patients at High Risk of Cardio Vascular Diseases (ISLE)

Immune Mediators and Metabolites to Stratify Systemic Lupus Erythematosus Patients at High Risk of Cardio Vascular Diseases

Immune Mediators and Metabolites to Stratify Systemic Lupus Erythematosus Patients at High Risk of Cardio Vascular Diseases

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/ the investigators identified specific immunometabolites (circulating nucleotide-derived metabolites adenine and N4-acetylcytidine), 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, the investigators propose that these immunometabolites may represent novel candidate biomarkers of CV risk stratification in SLE. 2/ the investigators 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) in a P-selectin/PSGL1 dependent manner. 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. The aim 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.

Proportion of patients who show atherosclerotic plaque progression defined by the absence of carotid plaque in patients at baseline and its subsequent development at follow-up evaluated by semi-automated 3D vascular ultrasound

Proportion of patients who show carotid Intima Media Thickness (cIMT) progression measured in the common carotid artery, at the bulb and the origin of the internal carotid artery

Change in lupus disease activity according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)

Change in lupus disease activity according to Systemic Lupus International Collaborating Clinics /American College of Rheumatology (SLICC/ACR) damage index

Change in platelets-derived biomarkers (P-selectin, sCD154) in micrograms per milliliter, evaluated by Western Blot analysis.

Change in neutrophils-derived biomarkers Proteins S100A8, A9, A8/9, and A12, IL-6 in micrograms per milliliter, evaluated by Western Blot analysis.

Change in myeloperoxidase-conjugated DNA levels in fluorescence intensity evaluated by fluorometric assay.

Inclusion Criteria: Adult patient aged over 18 years old. SLE diagnosis according to the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus Having signed an informed consent (at the latest on the day of inclusion and before any examination required by research). Exclusion Criteria: Pregnancy or breast-feeding for woman. Person concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent