Study of Neonatal IgG Fc Receptor Expression in Natural Killer T Cells Expressing an Invariant T Receptor : Implication in the Pathophysiology of Systemic Lupus

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Systemic Lupus Erythematosus, Physiopathology

Intervention / Treatment
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* Biological: Blood sample


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LUPUS PATIENTS<br>Three extra tubes of blood will be taken at each consultation or inpatient visit when routine blood samples are taken as part of lupus monitoring. | Biological: Blood sample<br>* Three extra tubes of blood will be taken at each consultation or inpatient visit when routine blood samples are taken as part of lupus monitoring.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FcRn Expression analysis in Circulating iNKT lymphocytes | by flow cytometry (mean fluorescence intensity) | through study completion, an average of 3 year | 
| FcRn Expression analysis in circulating monocytes | by flow cytometry (mean fluorescence intensity) | through study completion, an average of 3 year | 
| FcgammaRII Expression analysis in Circulating iNKT lymphocytes | by flow cytometry (mean fluorescence intensity) | through study completion, an average of 3 year | 
| FcgammaRII Expression analysis in circulating monocytes | by flow cytometry (mean fluorescence intensity) | through study completion, an average of 3 year | 
| FcgammaRIII Expression analysis in Circulating iNKT lymphocytes | by flow cytometry (mean fluorescence intensity) | through study completion, an average of 3 year | 
| FcgammaRIII Expression analysis in in circulating monocytes | by flow cytometry (mean fluorescence intensity) | through study completion, an average of 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| corticotherapy | data collected from patient medical file | through study completion, an average of 3 year | 
| hydroxychloroquine | data collected from patient medical file | through study completion, an average of 3 year | 
| immunosuppressants outside of biotherapy: methotrexate, azathioprine, mycophenolate mofetil | data collected from patient medical file | through study completion, an average of 3 year | 
| biotherapy: belimumab and rituximab | data collected from patient medical file | through study completion, an average of 3 year | 
| lupus disease activity | assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). The score ranging from 0 (no activity) to 105 | through study completion, an average of 3 year | 
| albumin and IgG levels | by immunonephelometry | through study completion, an average of 3 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lupus