Prognosis Assessment of the Increase of GADD34 Gene Expression for Patient Suffering From Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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Given that GADD34 has been described as a potential key regulator of pro-inflammatory cytokine production in human and elevated blood marker in SLE patients, this study aim to prove that the GADD34 RNA level in mononuclear blood cells can be used as a prognostic marker to assess the risk of SLE flare.

Detailed Description
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Systemic lupus erythematosus (SLE) has a prevalence estimated between 1 and 6 per 10000 individuals and concerns over 30 000 patients in France for example. As of today, there isn't any reliable specific blood analysis that can be used to assess the prognosis of SLE, that means predict a SLE flare. The discovery of such a blood test could allow a better patients' monitoring in order to help doctors to better adapt treatments (lowering background treatments when they are not needed and increase them ahead of a potential flare when the risk assessment raises). In SLE patients, a recent study shows elevated levels of GADD34 RNA in mononuclear blood cells : higher than twice the control levels for 36 of the 60 SLE patients and ten times higher than the control levels for 13 of the 60 SLE patients. Given that GADD34 has been described as a potential key regulator of pro-inflammatory cytokine production in human and elevated blood marker in SLE patients, this study aim to prove that the GADD34 RNA level in mononuclear blood cells can be used as a prognostic marker to assess the risk of SLE flare.

Official Title
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Prognosis Assessment of the Increase of GADD34 Gene Expression for Patient Suffering From Systemic Lupus Erythematosus

Conditions
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Lupus Erythematosus

Intervention / Treatment
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* Other: GADD34 RNA level measurement.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: man and women over 18 Years old. suffering from SLE (American College of Rheumatology criteria). without SLE flare for 3 months. with a signed consent and social security affiliation (required in France). Exclusion Criteria: Viral infection within 15 days. Other chronic inflammatory disease. People with special protection (defined in articles : L1121- §5-8 et 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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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group<br>250 SLE patients : All SLE patients included in the study. Intervention : Blood analysis including GADD34 RNA level measurement every 3 months up to 1 year. They will provided a blood sample every 3 months during a year. The result of GADD34 RNA level in mononuclear blood cells will be correlated to the clinical assessment of a SLE flare during the next 3 months. A flare occurence will the group | Other: GADD34 RNA level measurement.<br>* Blood analysis including GADD34 RNA level measurement is performed every 3 months up to 1 year for SLE patients. A modal including physical exam, standard biological results and GADD34 RNA level is correlated to a SLE flare occurence in the next 3 months.<br>* Other names: Experimental: Test group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GADD34 RNA level | GADD34 RNA level in mononuclear blood cells in the last 3 months before a SLE flare occurence. RNA levels have no unit,they are rates compared with a housekeeping gene RNA level as unit. To avoid any bias in primary outcome, SLE Flare occurence is assessed with both patient and investigator blinded from Gadd34 RNA level. | Measured every 3 months, up to 1 year (5 blood samples).The Last result before a SLE flare occurence will be used. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prognosis score of SLE flare occurence | Prognosis score of SLE flare occurence using a modal including GADD34 RNA increase, SLEDAI score and Physician Global Assessment (PGA). This modal is compared to the gold standard modal which use only PGA and SLEDAI Score in term of sensibility and specificity. | Measured every 3 months, up to 1 year (5 blood samples).The Last result before a SLE flare occurence will be used. | 
| Pro-inflammatory cytokine blood level. | Correlation between GADD34 RNA increase or decrease and interferon-alpha, interferon-beta, interleukin-6 and interleukine-17 levels. | Measured every 3 months, up to 1 year (5 blood samples). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Flare, Therapeutic adjustments, Biological Marker, Immunologic Marker, Prognosis