ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1903

PIK3CD Overexpression In The Synovial Membrane Of Rheumatoid Arthritis Patients Is Associated With Response To Anti-TNF Therapy

Antonio Julià1, Gabriela Ávila1, Raquel Celis2, Raimon Sanmarti3, Julio Ramirez4, Sara Marsal1 and Juan D. Cañete3, 1Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain, 2Arthritis Unit, Rheumatology Department, Arthritis Unit, Rheumatology Dpt, Hospital Clinic of Barcelona and IDIBAPS, Barcelona, Spain, 3Arthritis Unit. Rheumatology Department, Hospital Clínic of Barcelona, Barcelona, Spain, 4Rheumatology, Hospital Clinic, Barcelona, Spain

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Genetics and Genomics of Rheumatic Disease II

Session Type: Abstract Submissions (ACR)

Background/Purpose:

The mechanisms by which Rheumatoid Arthritis (RA) patients do not respond to TNF blockade are still poorly characterized. The goal of this study is to identify in synovial tissue (ST) of RA patients the genes that best characterize the profile of response to anti-TNF, therapy by using whole genome gene expression analysis. 

Methods:

Whole genome expression analysis of >21,000 genes was performed using Illumina WG-6 BeadChip microarrays in ST obtained by arthroscopy of RA patients before starting anti-TNF therapy. The clinical response was determined after 20 weeks of therapy using the EULAR criteria. The genes most significantly associated with the anti-TNF response were validated by quantitative RT-PCR. Changes in ST protein expression induced by anti-TNF therapy were quantified by immunochemistry and Digital Image Analysis. 

Results:

Eleven RA patients were included and a total of 135 genes were found to be differentially expressed between responders and non-responders after multiple test correction. The functional analysis of the overexpressed genes in the non-responder group (n=76 genes) identified a highly significant enrichment of genes expressed in peripheral blood CD14+ monocytes (similarity score Kappa=1.00, P=3.56e-5). We validated by RT-PCR the genes showing the most significant differential expression:  PIK3CD (P=7.11E-18) and CX3CL1 (P=7.39E-12). Synovial tissue expression of PIK3CD protein before and after 5 months of anti-TNF therapy showed a significant reduction (P=0.035) only in those patients with a positive clinical response.

Conclusion: Our findings suggest that PIK3CD could be a useful biomarker of response to TNF blockade.

Disclosure:

A. Julià,
None;

G. Ávila,
None;

R. Celis,
None;

R. Sanmarti,
None;

J. Ramirez,
None;

S. Marsal,
None;

J. D. Cañete,
None.

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