Interleukin-15 as a Biomarker Candidate of Rheumatoid Arthritis Development.

Weronika Kurowska,Wlodzimierz Maslinski,Brygida Kwiatkowska,Michal Jakubaszek,Malgorzata Przygodzka

doi:10.3390/jcm9051555

Abstract

There is a need for definite diagnosis of rheumatoid arthritis (RA) at its earliest stages of development in order to introduce early and effective treatment. Here we assessed whether serum interleukin-15 (IL-15) can serve as a new biomarker of RA development in patients with undifferentiated arthritis (UA). Interleukin-15, IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) were measured in UA patients at inclusion. Six months later, the diagnosis was re-evaluated, and statistical analysis was performed. We found that at the UA stage, IL-15 was more prevalent in patients who progressed to RA than RF or anti-CCP Abs (83.3% vs. 61.1% and 66.7%, respectively). Interleukin-15 showed higher sensitivity (77.8%) than both autoantibodies and higher specificity (80.9%) than anti-CCP Abs in identification of UA patients who developed RA. The diagnostic utility of IL-15 was comparable to that of RF (AUC: 0.814 vs. 0.750, p > 0.05), but higher than that of anti-CCP Abs (AUC: 0.814 vs. 0.684, p = 0.04). The combined use of IL-15, RF and anti-CCP Abs yielded higher diagnostic accuracy for RA than autoantibodies determination only. Our results indicate that IL-15 can be used as a biomarker of RA development in patients with UA.

Highlights

Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide affecting up to one percent of the adult population [1]
Recommended testing of anti-CCP Abs and rheumatoid factor (RF) levels can be insufficient for identification of patients who will progress to RA in the near future, as these autoantibodies can be present over years in asymptomatic subjects [18]
Increased levels of IL-15 were detected in serum, synovial fluid and bone marrow of RA patients compared to patients with other inflammatory arthropathies and/or osteoarthritis [21,22,23,24,25]

Summary

Introduction

Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide affecting up to one percent of the adult population [1]. The role of cytokines and autoantibodies in development of RA was studied in blood samples isolated a year to five years before the disease onset Even at this pre-RA stage, the serum levels of a large number of cytokines, chemokines, growth factors and autoantibodies were elevated in comparison to healthy people [11]. Our and others previous observations suggest that IL-15, one of the cytokines involved in pathogenesis of RA, could be a marker of RA development [13,14,15] Elevated levels of this cytokine were documented in RA and increased concentrations of IL-15 predicted severe disease course in patients with early RA or UA [13,14,15]. This study was undertaken to verify the hypothesis that, at the UA stage, IL-15 is a useful biomarker for identification of patients who will develop RA in the future

Patients

Measurement of Autoantibodies

Statistical Analysis

Patient Characteristics

Discussion