Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Affy Sjogren

ABSTRACT: Retuximab response transcription profiling in salivary glands from Sjogren patients

ORGANISM(S): Homo sapiens

SUBMITTER: Nicolas Cagnard

PROVIDER: E-MEXP-1883 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profile in the salivary glands of primary Sjögren's syndrome patients before and after treatment with rituximab.

Devauchelle-Pensec Valérie V Cagnard Nicolas N Pers Jacques-Olivier JO Youinou Pierre P Saraux Alain A Chiocchia Gilles G

Arthritis and rheumatism 20100801 8

<h4>Objective</h4>Primary Sjögren's syndrome (SS) is a complex disorder, in part due to B cell abnormalities. Although anti-B cell therapy is promising in primary SS, no treatment has yet been demonstrated to modify the disease course. This open-label study was undertaken to evaluate the efficacy of rituximab in primary SS and to investigate whether expression of specific genes is associated with efficacy of this treatment.<h4>Methods</h4>Fifteen patients with primary SS were treated in an open- ...[more]

PMID: 20506202

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Project description:Background: Results obtained from our previous study using a label-free quantitation (LF) proteomic approach in which dynamic range compression was used to profile lower abundance proteins, demonstrated few proteins that were differentially abundant within the synovial fluid (SF) when comparing Autologous Chondrocyte Implantation (ACI) responders and non-responders at baseline (1). This study builds upon our previous findings by assessing higher abundance proteins within these SFs; providing a more global proteome analysis from which we can understand more fully the biology underlying ACI success or failure. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomics was used to assess SFs from ACI responders (mean Lysholm improvement of 33; n=14) and non-responders (mean Lysholm decrease of 14; n=13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins were investigated using pathway analyses and the iTRAQ proteomic dataset was combined with our published proteomic dataset of dynamically compressed SFs, from which an interactome network model of systemic protein interactions was generated. Results: iTRAQ proteomics has confirmed our previous finding that there is a marked proteome shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥2.0 fold change between Stages I and II in responders and non-responders, respectively) and has highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, that were not found in the LF study; 16 of which were altered at baseline. Two protein abundance changes (Complement C1S subcomponent and Matrix metalloproteinase 3 (MMP3), have been biochemically validated. Combination of the iTRAQ and LF proteomic datasets has generated in-depth SF proteome information that has been used to generate interactome networks representing ACI success or failure, from which functional pathways that are dysregulated in ACI non-responders have been identified. Conclusions: Several candidate biomarkers for baseline prediction of ACI outcome have been identified. A holistic overview of the SF proteome in responders and non-responders to ACI has been profiled providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.

Dataset Information

Affy Sjogren

Publications

Gene expression profile in the salivary glands of primary Sjögren's syndrome patients before and after treatment with rituximab.

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