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

Summary

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.

Conditions

• Systemic Lupus Erythematosus

Interventions

BIOLOGICAL

blood sample

35 ml whole blood for Peripheral blood mononuclear cell (PBMC), serum and plasma

OTHER

Ultrasonography assessment

assessment of atherosclerotic plaques and measurement of carotid intima-media thickness (cIMT)

BEHAVIORAL

questionnaires

Food and exercise questionnaires validated by the American heart Association

Sponsors & Collaborators

• Foundation for Research in Rheumatology (FOREUM)

  collaborator UNKNOWN

• University Hospital, Bordeaux

  lead OTHER

Principal Investigators

• Pierre DUFFAU, Prof · University Hospital, Bordeaux

• Patrick BLANCO, Prof · University Hospital, Bordeaux

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-03-10

Primary Completion

2027-03-31

Completion

2027-03-31

Countries

• France
• Germany

Study Locations