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Ex vivo IL1Ra production upon LPS stimulation is associated with development of RA and with greater progression of joint damage
  1. J K De Vries-Bouwstra (jkdevriesbouwstra{at}
  1. VUmc, Netherlands
    1. Y PM Goekoop-Ruiterman
    1. LUMC, Netherlands
      1. J Wesoly
      1. LUMC, Netherlands
        1. H J Hulsmans
        1. Haga Hospital, Netherlands
          1. A JM de Craen
          1. LUMC, Netherlands
            1. F C Breedveld
            1. LUMC, Netherlands
              1. B AC Dijkmans
              1. VUmc, Netherlands
                1. C F Allaart
                1. LUMC, Netherlands
                  1. T WJ Huizinga
                  1. LUMC, Netherlands


                    Objectives: 1) To assess innate ex vivo production of interleukin 1β (IL1β) and IL1 receptor antagonist (IL1Ra) in patients with recent- onset rheumatoid arthritis (RA) as compared to healthy controls,

                    2) to assess the association of ex vivo IL1β and IL1Ra production with progression of joint damage in RA

                    3) to determine whether differences in ex vivo IL1β production are explained by distribution of the IL1β SNP C-511T.

                    Methods: Levels of IL1β and IL1Ra (measured by ELISA after whole-blood stimulation with lipopolysaccharide [LPS]), and distribution of IL1& [beta] C-511T were compared in 76 disease-modifying antirheumatic drug (DMARD)-naïve patients with recent- onset RA and 63 healthy controls. Odds ratios (OR) for RA based on ex vivo IL1β and IL1Ra production were calculated. Association of ex vivo IL1β and IL1Ra production with progression of joint damage (Sharp/vd Heijde score over 2 years) was determined by linear regression with correction for baseline characteristics.

                    Results: Patients with recent-onset RA showed lower ex vivo IL1β and higher ex vivo IL1Ra production than healthy controls (p<0.001), with OR for RA of 2.4 (95% confidence interval [CI] 1.2-4.9) for low IL1β-producers and 7.6 (95% CI 3.2-18.0) for high IL1Ra-producers. High ex vivo IL1Ra production was associated with joint damage progression (p=0.01). The IL1β C-511T genotype distribution was not significantly different between patients and controls.

                    Conclusions: Patients with recent-onset RA had decreased ex vivo IL1β production and increased ex vivo IL1Ra production compared to controls. Ex vivo IL1Ra production is an independent predictor of joint damage progression in recent-onset RA.

                    • genetics
                    • interleukin 1 beta
                    • interleukin 1 receptor antagonist
                    • joint damage
                    • rheumatoid arthritis

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