OP0266 Synovial tissue profiling in autoantibody positive at risk individuals reveals gene signatures associated with later development of rheumatoid arthritis
| Autor: | P.P. Tak, L G M van Baarsen, IY Choi, JF Semmelink, Danielle M. Gerlag, M J H de Hair |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Oncology
medicine.medical_specialty business.industry Autoantibody Arthritis 02 engineering and technology medicine.disease 020210 optoelectronics & photonics Median follow-up Rheumatoid arthritis Internal medicine Synovitis Cohort 0202 electrical engineering electronic engineering information engineering medicine Immunohistochemistry business Survival analysis |
| Zdroj: | FRIDAY, 15 JUNE 2018. |
| DOI: | 10.1136/annrheumdis-2018-eular.5148 |
| Popis: | Background Previous work has suggested subtle infiltration of synovial T cells1 in the absence of overt synovial inflammation2 in individuals at risk of developing rheumatoid arthritis (RA). Objectives To study the molecular changes in synovium preceding arthritis development in preclinical RA. Methods We included sixty-seven individuals who were IgM rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive and without any evidence of arthritis. All individuals underwent mini-arthroscopic synovial biopsy sampling of a knee joint at inclusion and were prospectively followed. First, an explorative genome-wide transcriptional profiling study was performed on synovial biopsies obtained from 13 individuals using Agilent arrays (test cohort). Survival analysis was used to identify transcripts with a significant association with arthritis development. The expression level of differentially expressed genes was validated using quantitative real-time PCR in the total cohort. Immunohistochemistry was used to study gene candidates at protein level in situ. Results Six of the 13 individuals in the explorative study developed RA after a median follow up time of 20 months (IQR 2–44). The 7 individuals who did not develop RA had a median follow up time of 85 months (IQR 69–86). Using a False Discovery Rate of Immunohistochemistry analyses (n=54) showed an abundant expression of CXCL12 and CXCR4 already in most RA-risk individuals. Synovial biopsies from RA-risk individuals who developed arthritis were more likely to show a positive gp38 staining and lower lipid staining. Conclusions This study clearly shows molecular changes appearing in synovial tissue before onset of arthritis in the absence of overt synovitis. Preclinical synovial alterations in immune response genes and lipid metabolism were associated with development of arthritis. References [1] de Hair MJ, et al. Arthritis Rheumatol2014. [2] van de Sande MG, et al. Ann Rheum Dis2011. Disclosure of Interest L. Van Baarsen: None declared, M. de Hair: None declared, J. Semmelink: None declared, I. Choi: None declared, D. Gerlag Employee of: GlaxoSmithKline, UK. GlaxoSmithKline was not involved in this study., P. Tak Employee of: GlaxoSmithKline, UK. GlaxoSmithKline was not involved in this study. |
| Databáze: | OpenAIRE |
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