Identification of intestinal biomarkers for evaluating disease activity in rheumatoid arthritis

To clarify the crucial prediction role of intestinal barrier markers - lipopolysaccharide binding protein (LBP), soluble cluster of differentiation 14 (sCD14), and intestinal fatty acid binding protein (I-FABP) - through combined diagnostics in rheumatoid arthritis (RA) patients.

A retrospective multi-centre study was conducted involving 139 RA patients from three hospitals, alongside 52 healthy controls (HCs). Serum levels of LBP, sCD14, and I-FABP were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical records were systematically collected, and receiver operating characteristic (ROC) analysis was performed to assess the predictive performance of the biomarkers.

Compared to HCs, serum levels of sCD14, LBP and I-FABP were significantly higher in RA patients (p<0.05). Among those, sCD14 levels demonstrated a significant positive correlation with disease activity score for 28 joints based on C-reactive protein (DAS28-CRP) (p=0.002), DAS28 based on erythrocyte sedimentation rate (DAS28-ESR) (p=0.048) and inflammatory index. I-FABP also exhibited a positive association with DAS28-ESR (p=0.027). The triad of biomarkers demonstrated a superior diagnostic capability for distinguishing RA from HCs (area under the curve [AUC]=0.936; p<0.001) and contributed to the reliability of disease activity prediction, yielding an AUC of 0.804. Notably, sCD14 levels emerged as an independent predictor of synovitis (odds ratio: 1.834, 95% confidence interval: [1.160-2.901], p=0.009).

Intestinal barrier-related biomarkers are associated with disease activity in RA. The combined assessment of LBP, sCD14, and I-FABP demonstrates good performance in differentiating RA from HCs and in evaluating disease activity. Furthermore, sCD14 may serve as a potential indicator of active synovitis, highlighting the clinical value of these biomarkers as complementary tools for disease assessment.