Neuron-specific Humoral and Cellular Immune Correlates of Structural and Functional Brain Connectomics in Neuropsychiatric Lupus

Neuron-specific Humoral and Cellular Immune Correlates of Structural and Functional Brain Connectomics in Neuropsychiatric Lupus

Systemic lupus erythematosus (SLE) is the prototype systemic autoimmune disease. Neuropsychiatric SLE (NPSLE) is a major cause of morbidity. Its pathophysiology remains unclear and target autoantigens have not yet been identified. Site- specific autoantigen expression might correlate with imaging abnormalities. Based on existing expertise on the use of peptide/protein arrays and on antigen-specific T cell tracking, we plan to identify new fingerprints and targets for NPSLE. SLE patients +/- NPSLE and healthy subjects will undergo advanced magnetic resonance imaging. Three-dimensional data on structural or functional brain architecture will be integrated with brain transcriptome atlases and candidate antigens for autoreactive autoantibodies and T lymphocytes identified and validated. The evidence will add to current knowledge on NPSLE pathophysiology, provide new multimodal diagnostic tools for better patient care and a platform for innovative, personalized treatments.

Inclusion Criteria:

Patients with SLE

• Diagnosis of SLE according to the ACR 1997, SLICC 2012 or EULAR/ACR 2019 criteria
• age ≥ 18 years (reference centre)
• age 15-17 years (affiliated centre)

Healthy subjects

• Charlson's Comorbidity Index=0 and no chronic treatment
• age ≥ 18 years (reference centre)
• age 15-17 years (affiliated centre)

Exclusion Criteria:

• History of T-cell neoplasia
• Active B-cell neoplasia or history of B-cell neoplasia of less than five years
• Contraindications to MRI
• Pregnancy
• Ongoing or past treatment with T-depleting agents
• History of brain cancer
• History of congenital brain disorders
• Cerebral disorders secondary to trauma, toxins or other metabolic or environmental factors unrelated to SLE according to the Investigator's evaluation
• Any other condition conferring excessive physical and psychological risk to the subject according to the Investigator's opinion