Clinical trial NCT05859191: Study of Neonatal IgG Fc Receptor Expression in Natural Killer T Cells Expressing an Invariant T Receptor : Implication in the Pathophysiology of Systemic Lupus
Official title: Study of Neonatal Immunoglobulin G (IgG) Fc Receptor (FcRn) Expression in Natural Killer T Cells Expressing an Invariant T Receptor (iNKT): Implication in the Pathophysiology of Systemic Lupus
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Systemic Lupus Erythematosus
Physiopathology
Keywords: lupus
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
Collaborators: name: Research Center for Respiratory Diseases, Inserm U1100
First posted: 2023-05-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with systemic lupus

Brief summary: This study evaluates the variation of expression of the neonatal Fc receptor (FcRn) in Natural Killer T Cells Expressing an Invariant T Receptor (iNKT) and monocytes along with the surface expression of Fc gamma type II receptor (RII) and RIII in active or newly diagnosed lupus patients compared to inactive lupus patients.

Detailed description: The role of FcRn in autoimmune diseases remains to be clarified, but it has been implicated in numerous pathophysiological mechanisms, notably in the management of immune complexes or the recycling of autoantibodies. In humans, this role in the metabolism of autoantibodies has recently led to the development of therapeutic antibodies for autoimmune diseases such as autoimmune thrombocytopenia and myasthenia.

The lupus erythematosus is an auto-immune disease mediated by IgG and immune complexes characterized by a high diversity of autoantibodies and a large dysregulation of the immune system in all it's components, one of them being iNKT cells.

Studies in patients or in lupus mouse models have shown a decrease in iNKT cells correlated with disease activity as well as tissue infiltration in relation to clinical manifestations. Their actual role in this pathology remains to be clarified between regulatory or pro-inflammatory effect.

The possible role of iNKT as a regulatory cell in lupus pathology and the possible involvement of FcRn in their development reinforces the interest of their simultaneous study in humans.

The aim of this study will be to evaluate the impact of the expression of FcRn and other Fc gamma receptors cooperating with FcRn (Fc gamma RII and RIII) in iNKT cells in lupus patients in relation to disease activity and therapy. This study will be conducted in parallel on monocytes, cells involved in the metabolism of immune complexes and likely to be activated by iNKT cells. These results will be compared to healthy controls and integrated into mechanistic studies in a mouse model.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Diagnosis of definite systemic lupus which may be associated with secondary antiphospholipid syndrome and/or secondary Gougerot-Sjögren's
* Lupus patient, newly diagnosed or known, untreated or in relapse
* Lupus patient considered stable by the treating practitioner
* Requiring blood sampling for follow-up

Exclusion Criteria:

* Main autoimmune disease other than lupus
* Patient under legal protection, guardianship or curators
* Opposition to data processing

Primary outcomes:
measure: FcRn Expression analysis in Circulating iNKT lymphocytes
timeFrame: through study completion, an average of 3 year
measure: FcRn Expression analysis in circulating monocytes
timeFrame: through study completion, an average of 3 year
measure: FcgammaRII Expression analysis in Circulating iNKT lymphocytes
timeFrame: through study completion, an average of 3 year
measure: FcgammaRII Expression analysis in circulating monocytes
timeFrame: through study completion, an average of 3 year
measure: FcgammaRIII Expression analysis in Circulating iNKT lymphocytes
timeFrame: through study completion, an average of 3 year
measure: FcgammaRIII Expression analysis in in circulating monocytes
timeFrame: through study completion, an average of 3 year
Secondary outcomes:
measure: corticotherapy
timeFrame: through study completion, an average of 3 year
measure: hydroxychloroquine
timeFrame: through study completion, an average of 3 year
measure: immunosuppressants outside of biotherapy: methotrexate, azathioprine, mycophenolate mofetil
timeFrame: through study completion, an average of 3 year
measure: biotherapy: belimumab and rituximab
timeFrame: through study completion, an average of 3 year
measure: lupus disease activity
timeFrame: through study completion, an average of 3 year
measure: albumin and IgG levels
timeFrame: through study completion, an average of 3 year
Other outcomes:
Locations:
city: Tours
country: France
facility: University Hospital
Study officials:
affiliation: CHRU de Tours
name: Yanis RAMDANI
role: PRINCIPAL_INVESTIGATOR
References: