Clinical trial NCT05880121: Neuron-specific Humoral and Cellular Immune Correlates of Structural and Functional Brain Connectomics in Neuropsychiatric Lupus
Official title: Neuron-specific Humoral and Cellular Immune Correlates of Structural and Functional Brain Connectomics in Neuropsychiatric Lupus
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Systemic Lupus Erythematosus
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Istituto Giannina Gaslini
First posted: 2023-05-30
Enrollment: 200
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: see above

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: To detect regional brain functional abnormalities in patients with SLE through advanced magnetic resonance imaging (MRI).
timeFrame: 12 months (extensions allowed for existing images before study onset)
measure: To identify autoantigen-specific circulating antibodies associated with neuropsychiatric morbidity and imaging features in patients with SLE.
timeFrame: 12 months (extensions allowed for existing MRI images before study onset)
measure: To correlate antigen-specific CD4+ T-cell dynamics over time with the spectrum of SLE, NPSLE and associated MRI findings.
timeFrame: 12 months (extensions allowed for existing MRI images before study onset)
Secondary outcomes:
Other outcomes:
Locations:
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
References: