Interleukin-15 as a Biomarker Candidate of Rheumatoid Arthritis Development

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.

Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications

“…The level of IL-15 is increased in the serum and synovial fluid in the early stage of RA, and promotes the release of TNF-a and IL-17 to participate in T lymphatic activation and subsequent bone destruction. It can be used as an independent biomarker for the detection of early RA (169)(170)(171)(172). IL-27 secreted by macrophages has dual antiinflammatory and pro-inflammatory functions.…”

The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis

“…Nonetheless, its levels are elevated during disease [ 114 ] and strongly correlate with rheumatoid factor and ACPA levels [ 115 , 116 ]. Additionally, this interleukin is suspected of taking part in osteoclastogenesis [ 117 ], T cells activation and trafficking [ 115 , 116 ] and stimulating cytokines production. Studies have shown that blockade of IL-15 signal transduction leads to the limitation of autoreactive T cells response and proliferation and decreases in IL-1β, IL-6, IL-17, MMP-3, and, most importantly TNF-α [ 116 ].…”

Acquisition of New Migratory Properties by Highly Differentiated CD4+CD28null T Lymphocytes in Rheumatoid Arthritis Disease

“…The amount of this cell subset has been expanded in ageing and pathogenic situations, such as chronic viral infections and autoimmune diseases, being widely described in RA patients [ 4 ]. In RA disease, it has been shown that CD4+CD28 null T lymphocytes and IL-15 levels are significantly increased in the blood and synovial fluid of these patients, suggesting an active role of both of them in the maintenance of inflammation in the target tissue, which could be correlated with the immunopathology and clinical activity of the disease [ 9 , 10 , 11 , 12 ]. Based on all this, we decided to study the migratory capacity of these CD4+CD28 null T lymphocytes and the effect that IL-15 could have in this process.…”

“…In fact, elevated serum and synovial fluid levels of IL-15 have been detected in RA patients, suggesting an important role of this cytokine in disease immunopathology and a correlation with clinical activity [ 10 , 11 ]. As a result, IL-15 has been recently proposed as a biomarker candidate for prediction of the development of RA, especially in the early phase of disease [ 12 ].…”