GADD34 and Type I IFN Response Genes in SLE

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03206359

Acronym

GADD34-IFN

Enrollment

Registered

2017-07-02

Start date

2012-01-25

Completion date

2015-04-03

Last updated

2017-07-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Systemic Lupus Erythematosus

Keywords

Unfolded Protein Response, GADD34, Type I IFN, IFN response genes, Type II IFN, anti-DNA autoantibodies

Brief summary

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.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

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)

Design outcomes

Primary

Measure	Time frame	Description
GADD34 expression in SLE patients	4 years	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

Secondary

Measure	Time frame	Description
GADD34 and IFN response gene expression	4 years	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
GADD34 expression and pathology activity	4 years	Evaluation of the relation between GADD34 overexpression and the activity of the pathology
CHOP and BiP expression	4 years	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.

Outcome results