Increased galectin-3 may serve as a serologic signature of pre-rheumatoid arthritis while markers of synovitis and cartilage do not differ between early undifferentiated arthritis subsets

Abstract

BackgroundUndifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings.MethodsOne hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets.ResultsGalectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6 μg/l, interquartile range (IQR) 3.8–5.5) versus non-RA (4.0 μg/l, IQR 3.1–4.9; p = 0.03) and controls (3.8 μg/l, IQR 3.0–4.8; p = 0.009). PIIANP was equally depressed in either subset (p < 0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls. In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema score, while PIIANP correlated with the MRI erosion score, and HYA with the synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3 discriminated well between pre-RA and non-RA with univariate area under the curve (AUC) of 0.64 (95% confidence interval (CI) 0.53–0.76) while AUC for galectin-3 + anti-CCP increased to 0.71 (95% CI 0.59–0.83).ConclusionsGalectin-3 in serum was increased in patients with early UA of pre-RA origin. Cartilage remodeling assessed by PIIANP was diminished in UA irrespective of subsequent clinical differentiation, while HYA did not differ from controls. ROC analysis showed a potential for galectin-3 to discriminate between pre-RA and non-RA.Trial registrationKF 11 315829. Registered 25 July 2006.

Galectin‐3 is Persistently Increased in Early Rheumatoid Arthritis (RA) and Associates with Anti‐CCP Seropositivity and MRI Bone Lesions, While Early Fibrosis Markers Correlate with Disease Activity

“…In their small series of long‐standing RA patients, these authors found that galectin‐3 was increased in synovial fluid and serum compared with osteoarthritis patients and healthy controls. In addition, our group has recently reported that galectin‐3 is higher in pre‐RA than in early, undifferentiated arthritis of non‐RA origin . Additional experimental research has provided further evidence for a role of galectin‐3 in the RA disease pathway.…”

Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z

“…Gal-3 was reported to contribute to the activation of RA synovial fibroblasts [ 377 ] and to promote the production of pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, in synovial fibroblasts [ 381 , 382 ]. For all these reasons the Gal-3 serum level was proposed as a predictive marker of future RA [ 383 ]. According to this study, the increase of serum levels of Gal-3 may help in discriminating between patients with undifferentiated arthritis who subsequently developed RA and those with undifferentiated arthritis who do not develop RA and in this sense it works better than other serological markers of cartilage regeneration (such as the type IIA collagen N-terminal propeptide, PIIANP) or synovial swellings (such as the hyaluronan, HYA).…”

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

“…Gal-3 has been reported to be expressed and secreted by inflamed synovium in patients of rheumatoid arthritis and osteoarthritis. Issa and colleagues reported that Gal-3 serum levels was persistently increased in early rheumatoid arthritis, and a positive correlation was observed between Gal-3 serum levels and some associated pathophysiology, such as autoimmunity, smoking, and joint destruction [72,120]. In experimental animal models for osteoarthritis, Gal-3 has been demonstrated to induce joint swelling and osteoarthritis-like lesions after intra-articular injection [119].…”