Interleukin 15 Levels in Serum May Predict a Severe Disease Course in Patients with Early Arthritis

Abstract

BackgroundInterleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA).Methodology and ResultsData from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06–0.18]; p<0.001) or ACPA (0.34 [0.01–0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18–2.7; p = 0.007).ConclusionsPatients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for patients that are candidates for early and more intensive treatment.

Enhanced and persistent levels of interleukin (IL)-17+CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis

“…IL-17 levels decreased following disease onset, while MCP-1, MIP-1α, GM-CSF and G-CSF were increased significantly in pre-patients compared with control subjects, and a number of other cytokines became increased significantly versus controls in the 3 years prior to disease onset (IL-2R, IL-1β, IL-9, IL-10, eotaxin, GM-CSF). Other studies have also demonstrated increased IL-15 in early arthritis, which may be associated with disease severity [30,31]. The increase in serum IL-4 demonstrated in EIA and RA is perhaps surprising.…”

Targeting the synovial angiogenesis as a novel treatment approach to osteoarthritis

“…IL-15 was consistently detectable and elevated in the serum of patients with early stage OA, compared with end-stage patients undergoing total knee replacement [Scanzello et al 2009]. Serum IL-15 detected by a proteomic approach was associated with the presence and progression of radiographic OA [Gonzalez-Alvaro et al 2011]. IL-15 may stimulate MMP production and recruitment or survival of CD8+ T cells within the OA joint.…”

Therapeutic potential of IL-15 in rheumatoid arthritis

“…IL-15 induces NK cells activation, measured either by direct cytotoxicity, antibody-dependent cellular cytotoxicity or cytokines production [36]. It has also been shown that IL-15 stimulates the functional maturation of DCs and IL-15 enhances the ability of DCs to activate CD8+ cells and NK cells by up-regulating the expression of co-stimulatory molecules and IFN-γ [37,38]. In addition, IL-15 enhances phagocytosis and protects from apoptosis of neutrophils, and affects mast cell proliferation [37].…”