GADD34 and Type I IFN Response Genes in SLE

Study Overview
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Brief Summary
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GADD34 (Growth Arrest and DNA Damage inducible-protein) is a regulatory subunit of PP1 (phosphatase 1) phosphatase which dephosphorylates eIF2alpha (eucaryotic initiation factor 2 alpha subunit), representing a negative feedback loop of the unfolded protein response (UPR). Moreover, GADD34 is necessary for type I interferon (IFN) production in response to viral infection in murine models. We investigate here the expression of GADD34 in systemic lupus erythematosus (SLE), in which type I IFN has an important pathogenic role. We report a case-control study on GADD34 gene expression in PBMC (peripheral blood mononuclear cells) of SLE patients (n=60) and age- and sex-matched healthy controls (n=30). The level of GADD34 gene expression, as well as of type-I IFN response genes in PBMC is measured by quantitative PCR.

Official Title
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Evaluation of GADD34 and Type I IFN Response Gene Expression in Patients Suffering From Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man and woman over 18 years old. Patients suffering from SLE (SLICC criteria) Patients having given their Non-opposition Patients with social security affiliation (required in France) Exclusion Criteria: Patients suffering from other auto-immune disease (except SAPL, thyroiditis, and Gougerot Sjogren syndrome) Patients with viral infection within 15 days People with special protection (defined in articles L1121-§5-8 and articles L3212-§1-3 of French health care law)

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 |
| --- | --- |
| Patients<br>Patients with SLE | |
| Healthy subjects<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GADD34 expression in SLE patients | Evaluation of GADD34 expression in PBMC of patients suffering from SLE compared to GADD34 expression in PBMC of healthy subjets. GADD34 gene expression level is quantified in the PBMC by quantitative PCR | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GADD34 and IFN response gene expression | Evaluation of the relation between IFN response gene expression and GADD34 expression in PBMC of patients suffering from SLE. IFN response gene and GADD34 expression level is quantified in the PBMC by quantitative PCR | 4 years | 
| GADD34 expression and pathology activity | Evaluation of the relation between GADD34 overexpression and the activity of the pathology | 4 years | 
| GADD34 expression and pathology activity | Evaluation of the relation between GADD34 overexpression and the presence of anti-DNA antibodies. | 4 years | 
| CHOP and BiP expression | Evaluation of the expression of other genes of UPR (like CHOP and BiP) in PBMC of patients with SLE, compared to the expression of these genes in PBMC of healthy subjets. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unfolded Protein Response, GADD34, Type I IFN, IFN response genes, Type II IFN, anti-DNA autoantibodies