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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-A00493-46 | Other Identifier | ID RCB |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test group | Experimental | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GADD34 RNA level measurement. | Other | 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. |
| 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. |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| GADD34 RNA level in each mononuclear blood cells (B cells, T cells and monocytes). | GADD34 RNA level is measured respectively in B cells, T cells and monocytes and is compared with each other. RNA levels have no unit,they are rates compared with a housekeeping gene RNA level as unit. This outcome is measured only for 30 patients. | Measured once at the 2nd visit (3 months after the inclusion). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Yves Cesbron, MD | University Hospital of Grenoble, France. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Grenoble | Grenoble | 38000 | France | |||
| groupement hospitalier mutualiste de Grenoble |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23584529 | Result | Claudio N, Dalet A, Gatti E, Pierre P. Mapping the crossroads of immune activation and cellular stress response pathways. EMBO J. 2013 May 2;32(9):1214-24. doi: 10.1038/emboj.2013.80. Epub 2013 Apr 12. | |
| 22615568 | Result | Clavarino G, Claudio N, Couderc T, Dalet A, Judith D, Camosseto V, Schmidt EK, Wenger T, Lecuit M, Gatti E, Pierre P. Induction of GADD34 is necessary for dsRNA-dependent interferon-beta production and participates in the control of Chikungunya virus infection. PLoS Pathog. 2012;8(5):e1002708. doi: 10.1371/journal.ppat.1002708. Epub 2012 May 17. |
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No data will be be shared with non associated investigator till publication. Possibility to share after publication, through formol requirement adressed to Grenoble hospital administration (AccueilRecherche@chu-grenoble.fr)
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| 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). |
| GADD34 RNA level in non-mononuclear blood cells | GADD34 RNA level is measured respectively in non-mononuclear blood cells and is compared with GADD34 RNA level in mononuclear blood cells. RNA levels have no unit,they are rates compared with a housekeeping gene RNA level as unit. This outcome is measured only for 30 patients. | Measured once at the 2nd visit (3 months after the inclusion). |
| Grenoble |
| 38000 |
| France |
| Hopital européen de Marseille | Marseille | 13003 | France |
| CHU Marseille | Marseille | 13005 | France |
| CHR Annecy Genevois | Metz-Tessy | 74370 | France |
| CHU Lyon sud | Pierre-Bénite | 69310 | France |
| CHU Saint Etienne | Saint-Etienne | 42000 | France |
| 22315398 | Result | Clavarino G, Claudio N, Dalet A, Terawaki S, Couderc T, Chasson L, Ceppi M, Schmidt EK, Wenger T, Lecuit M, Gatti E, Pierre P. Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3006-11. doi: 10.1073/pnas.1104491109. Epub 2012 Feb 6. |
| 23144449 | Result | Costedoat-Chalumeau N, Galicier L, Aumaitre O, Frances C, Le Guern V, Liote F, Smail A, Limal N, Perard L, Desmurs-Clavel H, Boutin du LT, Asli B, Kahn JE, Pourrat J, Sailler L, Ackermann F, Papo T, Sacre K, Fain O, Stirnemann J, Cacoub P, Jallouli M, Leroux G, Cohen-Bittan J, Tanguy ML, Hulot JS, Lechat P, Musset L, Amoura Z, Piette JC; Group PLUS. Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study). Ann Rheum Dis. 2013 Nov;72(11):1786-92. doi: 10.1136/annrheumdis-2012-202322. Epub 2012 Nov 10. |
| 20652065 | Result | Niewold TB, Clark DN, Salloum R, Poole BD. Interferon alpha in systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:948364. doi: 10.1155/2010/948364. Epub 2010 Jun 29. |
| 11381086 | Result | Novoa I, Zeng H, Harding HP, Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol. 2001 May 28;153(5):1011-22. doi: 10.1083/jcb.153.5.1011. |
| 23754628 | Result | Petri MA, van Vollenhoven RF, Buyon J, Levy RA, Navarra SV, Cervera R, Zhong ZJ, Freimuth WW; BLISS-52 and BLISS-76 Study Groups. Baseline predictors of systemic lupus erythematosus flares: data from the combined placebo groups in the phase III belimumab trials. Arthritis Rheum. 2013 Aug;65(8):2143-53. doi: 10.1002/art.37995. |
| 12480667 | Result | Ronnelid J, Tejde A, Mathsson L, Nilsson-Ekdahl K, Nilsson B. Immune complexes from SLE sera induce IL10 production from normal peripheral blood mononuclear cells by an FcgammaRII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE. Ann Rheum Dis. 2003 Jan;62(1):37-42. doi: 10.1136/ard.62.1.37. |
| 22733998 | Result | Wang S, Kaufman RJ. The impact of the unfolded protein response on human disease. J Cell Biol. 2012 Jun 25;197(7):857-67. doi: 10.1083/jcb.201110131. |
| 23452295 | Result | Yap DY, Lai KN. The role of cytokines in the pathogenesis of systemic lupus erythematosus - from bench to bedside. Nephrology (Carlton). 2013 Apr;18(4):243-55. doi: 10.1111/nep.12047. |