Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort

Abstract

Background Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients who do or do not develop clinically evident inflammatory arthritis (IA). Methods Two hundred thirty-six consecutive patients presenting with arthralgia clinically suspected for progression to RA were followed until IA development or else for median 24 months (IQR 12–26). Baseline whole blood RNA expression was determined for a previously identified set of 133 genes associated with the innate and adaptive immune system by dual-color reverse-transcription multiplex ligation-dependent probe amplification (dcRT-MLPA) profiling. Cox proportional hazard models were used. Results Twenty percent of CSA patients developed IA. After correction for multiple testing, expression levels of six genes (IFNG, PHEX, IGF-1, IL-7R, CD19, CCR7) at the time of presentation were associated with progression to IA. PHEX and IGF-1 were highly correlated with each other (ρ = 0.97). In multivariable analysis correcting for the different genes, expressions of IL-7R and IGF-1 were independently associated with IA development (p = 0.025, p = 0.046, respectively). Moreover, IL-7R and IGF-1 remained significantly associated even after correction for known predictors (ACPA, CRP, imaging-detected subclinical joint inflammation; p = 0.039, p = 0.005, respectively). These genes are also associated with RA development. Conclusions IL-7R and IGF-1 were differentially expressed between CSA patients who did or did not progress to IA, independent from regularly used predictors. These biomarkers may become helpful in prognostication of CSA patients. Furthermore, because both genes are associated with T cell functioning, T cell dysregulation may mediate progression from arthralgia to arthritis.

Gene Expression Profiles Analyzed Using Integrating RNA Sequencing, and Microarray Reveals Increased Inflammatory Response, Proliferation, and Osteoclastogenesis in Pigmented Villonodular Synovitis

“…C-C motif chemokine ligand 20 recruits the pro-inflammatory interleukin (IL)-17–producing helper T cells 17 and the regulatory T cells, and thereby contributes to the chemotaxis of DC and neutrophils ( 23 , 24 ). IL-7R, a receptor of IL-7, combines with IL-2R to play a vital role in V(D)J recombination during the development of lymphocytes ( 25 ).…”

Perceptions and experiences of individuals at-risk of rheumatoid arthritis (RA) knowing about their risk of developing RA and being offered preventive treatment: systematic review and thematic synthesis of qualitative studies

“…4 Research regarding the early diagnosis of RA has resulted in prediction models and international classification criteria, [5][6][7][8][9] and there is an increasing focus on the efficacy of preventive medication in the preclinical phase to prevent or delay the progression of RA. [10][11][12][13][14] However, there is limited insight into how at-risk individuals understand their own risk and on their views regarding predictive testing and engaging with preventive interventions, including lifestyle changes and medication. A metasynthesis of qualitative studies exploring the perceptions of predictive testing for those at-risk of developing a chronic inflammatory disease has previously been conducted.…”

Gene Expression Profiles Analyzed Using Integrating RNA Sequencing and Microarray Reveals Increased Inflammatory Response, Proliferation, and Osteoclastogenesis in Pigmented Villonodular Synovitis

“…C-C motif chemokine ligand 20 recruits the proin ammatory interleukin (IL)-17 producing helper T cells 17 and the regulatory T cells, and thereby contributes to the chemotaxis of DC and neutrophils (23,24). IL-7R, a receptor of IL-7, combines with IL-2R to play a vital role in V(D)J recombination during the development of lymphocytes (25).…”