Higher expression of TNFα-induced genes in the synovium of patients with early rheumatoid arthritis correlates with disease activity, and predicts absence of response to first line therapy

Arthritis Research & Therapy
Aurélie De GroofB R Lauwerys

Abstract

IL6-related T cell activation and TNFα-dependent cell proliferation are major targets of therapy in the RA synovium. We investigated whether expression of these pathways in RA synovial biopsies is associated with disease activity and response to therapy. Correlation and gene set enrichment studies were performed using gene expression profiles from RA synovial biopsies. Immunostaining experiments of GADD45B and PDE4D were performed on independent additional sets of early untreated RA samples, obtained in two different centers by needle-arthroscopy or US-guided biopsies. In 65 RA synovial biopsies, transcripts correlating with disease activity were strongly enriched in TNFα-induced genes. Out of the individual variables used in disease-activity scores, tender joint count, swollen joint count and physician's global assessment, but not CRP or patient's global assessment displayed a similar correlation with the expression of TNFα-dependent genes. In addition, TNFα-induced genes were also significantly enriched in transcripts over-expressed in synovial biopsy samples obtained from poor-responders to methotrexate or tocilizumab, prior to initiation of therapy. GADD45B (induced by TNFα in monocytes) and PDE4D (induced by TNFα in FLS) i...Continue Reading

References

May 27, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Fang DuNingli Li
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Oct 31, 2009·Arthritis and Rheumatism·Camilla I SvenssonGary S Firestein
May 23, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Biljana SmiljanovicAndreas Grützkau
Mar 16, 2013·Current Opinion in Rheumatology·Costantino PitzalisFrances Humby
Jan 23, 2014·Arthritis & Rheumatology·Julie DucreuxBernard R Lauwerys
Aug 29, 2014·Arthritis Research & Therapy·Glynn DennisMichael J Townsend
May 1, 2015·PloS One·Bernard R LauwerysPierre Dupont

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Citations

Jun 15, 2019·Journal of Clinical Medicine·Ruei-Nian LiJeng-Hsien Yen
Dec 1, 2019·Arthritis & Rheumatology·Dana E Orange, Laura T Donlin
Apr 6, 2019·Frontiers in Medicine·Clément Triaille, Bernard R Lauwerys
Sep 6, 2020·Nature Reviews. Rheumatology·Costantino PitzalisMaya H Buch
Jul 30, 2021·International Journal of Rheumatic Diseases·Robert W Ike, Kenneth C Kalunian
Aug 24, 2021·Frontiers in Medicine·Francesca IngegnoliRoberto Caporali
Sep 17, 2021·Frontiers in Immunology·Clement TriailleNisha Limaye

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Datasets Mentioned

BETA
GSE45867
GSE15615
GSE73764

Methods Mentioned

BETA
biopsies
biopsy

Software Mentioned

GeneSpring
Excel
Frida

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