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

Systemic Lupus Erythematosus Clinical Trial

— FiNKLUPUS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05859191
• Other study ID #: DR230103-FiNK LUPUS
• Status: Recruiting
• Start date: July 21, 2023
• Est. completion date: July 2029

Study information

• Verified date: August 2023
• Source: University Hospital, Tours
• Contact: Yanis RAMDANI
• Phone: 0234378919
• Email: yanis.ramdani[@]univ-tours.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 2029
• Est. primary completion date: July 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Physiopathology
• Systemic Lupus Erythematosus

Intervention

Biological:
• Blood sample
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.

Locations

Country	Name	City	State
France	University Hospital	Tours

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Tours	Research Center for Respiratory Diseases, Inserm U1100

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FcRn Expression analysis in Circulating iNKT lymphocytes	by flow cytometry (mean fluorescence intensity)	through study completion, an average of 3 year
Primary	FcRn Expression analysis in circulating monocytes	by flow cytometry (mean fluorescence intensity)	through study completion, an average of 3 year
Primary	FcgammaRII Expression analysis in Circulating iNKT lymphocytes	by flow cytometry (mean fluorescence intensity)	through study completion, an average of 3 year
Primary	FcgammaRII Expression analysis in circulating monocytes	by flow cytometry (mean fluorescence intensity)	through study completion, an average of 3 year
Primary	FcgammaRIII Expression analysis in Circulating iNKT lymphocytes	by flow cytometry (mean fluorescence intensity)	through study completion, an average of 3 year
Primary	FcgammaRIII Expression analysis in in circulating monocytes	by flow cytometry (mean fluorescence intensity)	through study completion, an average of 3 year
Secondary	corticotherapy	data collected from patient medical file	through study completion, an average of 3 year
Secondary	hydroxychloroquine	data collected from patient medical file	through study completion, an average of 3 year
Secondary	immunosuppressants outside of biotherapy: methotrexate, azathioprine, mycophenolate mofetil	data collected from patient medical file	through study completion, an average of 3 year
Secondary	biotherapy: belimumab and rituximab	data collected from patient medical file	through study completion, an average of 3 year
Secondary	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
Secondary	albumin and IgG levels	by immunonephelometry	through study completion, an average of 3 year