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

Ellis Niemantsverdriet, Erik B. van den Akker, Debbie M. Boeters, Susan J.F. van den Eeden, Annemieke Geluk, Annette H.M. van der Helm-van Mil

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)
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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.

Original languageEnglish
Article number266
Number of pages7
JournalArthritis Research and Therapy
Volume22
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • Clinically suspect arthralgia
  • Gene expression
  • Inflammatory arthritis
  • MLPA
  • RNA

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