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

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.Pattern Recognition and Bioinformatic

Correction to: Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort (Arthritis Research & Therapy, (2020), 22, 1, (266), 10.1186/s13075-020-02361-2)

Following publication of the original article [1], a typesetting error was reported. The equal contribution note for this article was incorrect. The corrected statement is given below. † Ellis Niemantsverdriet and Erik B. van den Akker contributed equally and are joint first authors. † Annemieke Geluk and Annette H. M. van der Helm-van Mil contributed equally and are joint last authors. The original article [1] has been corrected.Pattern Recognition and Bioinformatic

Earlier chronotype in patients with rheumatoid arthritis

Objectives: Rheumatoid arthritis (RA) patients show an earlier circadian rhythm (i.e. serum melatonin peaks earlier during the night, indicating an earlier timing of the internal circadian pacemaker). In the current study, we examined whether the chronotype, which is influenced by the circadian rhythm, is also earlier. In addition, we explored whether chronotype is related to disease activity and patient-reported outcomes. Methods: The chronotype (Munich Chronotype Questionnaire) of patients with RA (n = 121; mean age 60 years, 73% female) was compared with that of subjects from the general population (norm group; n = 1695) with a one-sample t test. In addition, we investigated chronotype in relation to disease activity (Disease Activity Score; DAS), reported morning stiffness, fatigue (Checklist Individual Strength), and health-related quality of life (RAND-36). Results: The chronotype of patients with RA was, on average, 23 min (95% CI, 15 to 31 min) earlier than that of the norm group (t(115) = − 5.901, p < 0.001, d = 0.55). Chronotype was not related to disease activity or patient-reported outcomes (p > 0.05). Conclusion: As expected, chronotype was earlier in RA patients. However, in this correlational study, chronotype was not related to disease activity or patient-reported outcomes. An experimental study is needed to examine whether delaying the circadian rhythm has a positive influence on these outcomes. This insight could improve our understanding of the pathophysiology of RA and contribute to exploring new treatment possibilities.• This is the first study examining chronotype in patients with rheumatoid arthritis, and how chronotype relates to disease activity and patient-reported outcomes.• We found an earlier chronotype in patients with rheumatoid arthritis than in subjects from the general population.• In this correlational study, chronotype was not related to disease activity or patient-reported outcomes. An experimental study is needed to examine whether delaying the circadian rhythm positively influences these outcomes.HR HealthIndustrial Design EngineeringApplied Ergonomics and Desig

Automatic quantification of bone marrow edema on MRI of the wrist in patients with early arthritis: A feasibility study

Purpose: To investigate the feasibility of automatic quantification of bone marrow edema (BME) on MRI of the wrist in patients with early arthritis. Methods: For 485 early arthritis patients (clinically confirmed arthritis of one or more joints, symptoms for less than 2 years), MR scans of the wrist were processed in three automatic stages. First, super-resolution reconstruction was applied to fuse coronal and axial scans into a single high-resolution 3D image. Next, the carpal bones were located and delineated using atlas-based segmentation. Finally, the extent of BME within each bone was quantified by identifying image intensity values characteristic of BME by fuzzy clustering and measuring the fraction of voxels with these characteristic intensities within each bone. Correlation with visual BME scores was assessed through Pearson correlation coefficient. Results: Pearson correlation between quantitative and visual BME scores across 485 patients was r=0.83, P<0.001. Conclusions: Quantitative measurement of BME on MRI of the wrist has the potential to provide a feasible alternative to visual scoring. Complete automation requires automatic detection and compensation of acquisition artifacts.Pattern Recognition and Bioinformatic