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  1. F. Angeli1,
  2. S. Piantoni1,
  3. M. Passari2,
  4. S. Scutera3,
  5. V. Salvi2,
  6. T. Schioppa2,
  7. R. Sparti3,
  8. F. Sozio2,
  9. L. Tiberio2,
  10. D. Bosisio2,
  11. F. Acquati4,
  12. S. Sozzani5,
  13. T. Musso3,
  14. A. Del Prete2,
  15. L. Andreoli1
  1. 1ASST Spedali Civili of Brescia and University of Brescia, Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, Brescia, Italy
  2. 2University of Brescia, Department of Molecular and Translational Medicine, Brescia, Italy
  3. 3University of Turin, Department of Public Health and Pediatric Sciences, Turin, Italy
  4. 4University of Insubria, Department of Biotechnologies and Life Sciences, Varese, Italy
  5. 5Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, Rome, Italy


Background Circulating biomarkers with diagnostic and prognostic value in early Rheumatoid Arthritis (RA) are still an unmet need, especially for the subgroup of seronegative RA [e.g., negative for anti-citrullinated peptides autoantibodies (ACPA) and/or rheumatoid factors (RF)]. In a recent gene-based genome-wide association analysis (GWAS) study, RNASET2 was identified as a potential susceptibility gene [1-3]. Furthermore, the extracellular ribonuclease RNASET2 was demonstrated to be involved in the regulation of several immune processes [4].

Objectives The aim of this study was to analyse RNASET2 serum levels in a cohort of RA patients upon their disease activity, in comparison with healthy controls (HC).

Methods Forty consecutive patients with RA (75% female, 55% seropositive) with a median age (25th-75th percentile) of 55 years (45-68) and a CRP-DAS28 index of 3.09 (2.50-3.70), and 25 sex and age-matched HC were enrolled in the study. RNASET2 serum levels were assessed through a commercial hELISA test (WuHan Fine Biotech Co., China).

Results Serum levels of RNASET2 were higher in RA patients than in HC [29.42 (17.73 – 69.82) vs 18.15 (12.15 – 28.35) ng/mL; p= 0.001]. Among patients with RA, there were no differences between RNASET2 levels in seropositive or seronegative ones [33.14 (16.79 – 74.89) vs 29.01 (17.83 – 39.85) ng/mL; p=0.308]. Furthermore, there were no differences in RNASET2 serum levels between patients in treatment with corticosteroids or not [42.09 (18.11 – 78.78) vs 23.42 (18.29 – 43.87) ng/mL; p=0.239]. RNASET2 serum levels were significantly different across 3 groups of RA patients identified upon the CRP-DAS28 score (high plus moderate disease activity –group A-; low disease activity –group B-; remission –group C-) (p= 0.024). RNaseT2 levels were higher in both group A and B as compared to group C [56.73 (30.22 – 79.67) - 83.72 (52.68 – 113.89) vs 25.43 (20.15 – 39.85) ng/mL; p= 0.005 & p= 0.007]. No difference was found between group A & B. When combining groups A & B, RNASET2 levels were significantly higher than in group C [67.14 (36.07 – 86.68) vs 25.43 (20.15 – 39.85) ng/mL; p= 0.013]. No significant correlation was found between RNASET2 serum levels and CRP-DAS28 (r= 0.36; p= 0.055).

Conclusion This is the first description of circulating serum levels of RNASET2 as a potential diagnostic biomarker in RA. Higher levels of RNASET2 clustered in RA patients as compared to HC. Low levels of RNASET2 seem to characterize the remission phase of RA. These preliminary results deserve to be expanded in larger cohorts of RA patients, patients with other form of chronic arthritis and other pathological and healthy controls.

References [1]Zhu et al. PLOSone 2016;

[2]Walsh et al. Genome Biology 2016;

[3]Muaaz Aslam et al. Disease Markers 2020;

[4]Acquati et al. Frontiers Immunol 2019

Acknowledgements This work was supported by the Italian Ministry for University and Research (Prin 2017NTK4HY).

Disclosure of Interests None Declared.

  • Rheumatoid arthritis
  • Biomarkers

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