Baseline serum interleukin-34 levels independently predict radiographic progression in patients with rheumatoid arthritis

Abstract

The aim of our observational study was to investigate the clinical significance of interleukin (IL)-34, a novel osteoclastogenic cytokine, for predicting structural damage in patients with rheumatoid arthritis (RA). Serum IL-34 levels were measured in 100 RA patients, 36 patients with ankylosing spondylitis (AS), and 59 gender- and age-matched healthy individuals using an enzyme-linked immunosorbent assay. We also measured IL-34 concentrations in synovial fluid (SF) samples from 18 RA patients and 19 osteoarthritis (OA) patients. Progression of structural damage was assessed in 81 patients with RA by plain radiographs using the modified Sharp/van der Heijde score (SHS) at baseline and after an average 1.6-year follow-up period. Serum IL-34 levels were significantly higher in patients with RA (p < 0.001) or AS (p < 0.001) than in healthy controls. SF IL-34 levels were also significantly higher in RA patients than in OA patients (p < 0.001). In RA, serum IL-34 levels were associated with rheumatoid factor positivity (p = 0.01), current smoking (p < 0.01), erythrocyte sedimentation rate (p = 0.01), and C-reactive protein levels (p < 0.01), but not with disease activity score 28. ΔSHS/year was positively correlated with serum IL-34 levels (r = 0.443, p < 0.001). In multivariate logistic regression analyses, serum IL-34 level was an independent risk factor for radiographic progression. These results suggest that IL-34, a novel osteoclastogenic cytokine, plays a role in RA-associated joint damage and is a potential biomarker for predicting subsequent radiographic progression in patients with RA.

Joint Destruction and Osteoporosis are Associated with Upregulation of IL34 and Cathepsin k Expression in Rheumatoid Arthritis. Clinical Trial with Anti TNF α Therapy

“…This was in accordance with a recent study by Chang et al that baseline IL-34 levels were positively correlated to ΔSHS/year [49]. As it was previously confirmed that SHS was positively correlated with disease activity and local inflammation and this was similar to our findings [50].…”

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

“…With regard to experimental arthritis, it is interesting to note that the lack/blockade of CSF-1 as well as the blockade of CSF-1R is associated with less severe methylated bovine serum albumin (mBSA)-induced arthritis and CIA [146][147][148]. In RA patients, all available studies pointed to increased serum and SF levels of IL-34 with respect to normal and disease controls (OA, PsA, ankylosing spondylitis (AS)) [149][150][151][152][153]. Of interest, ser0075m IL-34 levels correlated with immunological markers of more severe disease including rheumatoid factor (RF), anticyclic citrullinated peptide antibody (anti-CCP) titers, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and with disease activity and smoking [149][150][151][152].…”

“…In RA patients, all available studies pointed to increased serum and SF levels of IL-34 with respect to normal and disease controls (OA, PsA, ankylosing spondylitis (AS)) [149][150][151][152][153]. Of interest, ser0075m IL-34 levels correlated with immunological markers of more severe disease including rheumatoid factor (RF), anticyclic citrullinated peptide antibody (anti-CCP) titers, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and with disease activity and smoking [149][150][151][152]. In this regard, serum IL-34 levels have been also associated with radiographic progression and appear to be good predictors of radiographic damage in RA patients [150,152].…”

“…Of interest, ser0075m IL-34 levels correlated with immunological markers of more severe disease including rheumatoid factor (RF), anticyclic citrullinated peptide antibody (anti-CCP) titers, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and with disease activity and smoking [149][150][151][152]. In this regard, serum IL-34 levels have been also associated with radiographic progression and appear to be good predictors of radiographic damage in RA patients [150,152]. Interestingly, treatment with DMARDs or TNF-α inhibitors is able to reduce serum IL-34 levels [151,154].…”

Interleukin-34: A Potential Diagnostic and Therapeutic Target for Rheumatoid Arthritis

“…It has been reported 1,5 that elevated levels of IL-34 have been observed in the joint tissue, serum, synovial fluid, and fibroblast-like synoviocytes of patients with RA. Interestingly, elevated levels of IL-34 were also detected in early RA (disease duration ≤ 6 mos) 2 and a significant association was found between IL-34 expression and synovitis severity 6 . Of greatest interest, significant positive correlations were found between IL-34 levels, inflammation variables (such as erythrocyte sedimentation rate and C-reactive protein), antibodies production (such as RF and anti-CCP), and disease activity indexes (such as tender joint count and the Disease Activity Score at 28 joints) 7 .…”