GADD34 and Type I IFN Response Genes in SLE

N/ACompletedNCT03206359

University Hospital, Grenoble90 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Systemic Lupus Erythematosus

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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

Time frame: 4 years

Secondary Outcomes

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

Time frame: 4 years

GADD34 expression and pathology activity

Evaluation of the relation between GADD34 overexpression and the activity of the pathology

Time frame: 4 years

GADD34 expression and pathology activity

Evaluation of the relation between GADD34 overexpression and the presence of anti-DNA antibodies.

Time frame: 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.

Time frame: 4 years