Identification of intestinal biomarkers for evaluating disease activity in rheumatoid arthritis

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.