ROLE of PLATELETS in the PATHOPHYSIOLOGY of SYSTEMIC LUPUS

University Hospital, Strasbourg, France450 enrolled

Overview

Blood platelets, well known for their role in hemostasis, are abnormally activated in patients suffering from systemic lupus erythematosus (SLE), but also from other immunomediated diseases (scleroderma, vasculitis, myositis, Gougerot-Sjögren's and rheumatoid arthritis) in cases of high disease activity. Once activated, platelets express adhesion molecules such as P-selectin on their surface, enabling them to interact physically with immune cells. In a recent work, we identified that activated platelets from lupus patients interact with regulatory T cells and block their regulatory function, thus participating in the deregulated activation of the immune system in SLE. In addition, inhibition of platelet-immune cell interactions by an anti-P-selectin antibody improved LES symptoms in two mouse models. The aim of this work is to investigate other potential platelet-immune cell interactions in patients with SLE, in comparison with other autoimmune diseases (systemic scleroderma, ANCA vasculitides, inflammatory myositis, Gougerot-Sjögren syndrome and rheumatoid arthritis). This study could lead to a better understanding of the role of platelets in the pathophysiology of autoimmune diseases, identify new biomarkers of activity, and assess the potential of new therapeutic avenues in these diseases, such as platelet targeting.

Study Type

OBSERVATIONAL

Enrollment

450

Conditions

Systemic Lupus Erythematosus Systemic Scleroderma Meeting ANCA Vasculitis Inflammatory Myositis

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients between 18 and 70 years of age * Patient affiliated to a health insurance scheme (beneficiary or beneficiary's beneficiary) * Patient able to understand the aims and risks of research * Patient having signed and dated an informed consent form * Patient for whom the diagnosis of at least one of the following pathologies has been confirmed: * Systemic lupus erythematosus meeting ACR/EULAR 20195 classification criteria. * Systemic scleroderma meeting ACR/EULAR 20136 classification criteria. * ANCA vasculitis according to EULAR/ACR 2022.7-9 classification criteria. * Inflammatory myositis according to EULAR/ACR 201710 classification criteria. * Gougerot-Sjögren syndrome according to EULAR/ACR 2016 classification criteria11. * Rheumatoid arthritis according to ACR/EULAR 201012 classification criteria. Exclusion Criteria: * Patient in exclusion period (determined by a previous or current study) * Inability to give patient informed consent (patient in emergency or immediate life-threatening situation) * Patient under court protection * Patient under guardianship or curatorship

Outcomes

Primary Outcomes

The primary endpoint will be the percentage of circulating aggregates between platelets and immune cells according to disease activity, assessed by flow cytometry.

Time frame: Every visit for 3 years

Secondary Outcomes

Phenotypic impact of platelet/immune cell interaction.

The impact of platelet/immune cell interaction will be assessed using flow cytometry on patient samples. Using a spectral cytometer (Aurora, Cytek) and a multi-color panel (45 colors), we will study the phenotype and degree of activation of different immune subpopulations according to whether or not they interact with platelets. This analysis will be carried out several times during the different visits, and mirrored with the disease activity criteria studied. Activation molecule expression will be analyzed using the same methods as for the main criterion (comparison of the patient with himself/herself using longitudinal samples).

Time frame: Every visit (each 6 months) for 3 years