IFABP2 as a new prognostic biomarker for secondary non-response in rheumatoid arthritis

Abstract

Increased intestinal permeability promotes the translocation of bacterial products from the local microbiome to the circulation, inducing inflammation and increasing clinical activity in rheumatoid arthritis (RA). This study evaluates whether intestinal fatty acid binding protein 2 (IFABP2) serum levels are prognostic biomarkers of non-response to conventional synthetic disease-modifying antirheumatic drug therapy (csDMARDs) in RA. The therapeutic schemes administered to 60 women with RA for at least 18months were assessed retrospectively, and the treatment response was classified according to the change in DAS28-ESR over time. Serum levels of IFABP2 and TNF-α were determined by ELISA. Receiver operating characteristics (ROC) curve analysis and logistic regression models were used to assess the predictive value and the association of IFABP2 with the non-responder phenotype in RA patients. Eleven women had a responder phenotype, 23 had a primary non-responder phenotype, and 26 had a secondary non-responder phenotype. Secondary non-responders showed higher DAS28-ESR (P=0.009) and higher IFABP2 serum levels compared to the responder group (P=0.023) and the primary non-responder group (P=0.018). IFABP2 serum levels were positively correlated with chloroquine dose (r=0.581, P=0.007) and negatively correlated with total cholesterol (r=-0.456, P=0.019) in secondary non-responders. The area under the curve (AUC) value of IFABP2 for predicting secondary non-response was 0.736, and IFABP2 serum levels>9.311ng/mL were associated with secondary non-response to csDMARDs (OR=6.00, P=0.003). IFABP2 serum levels are potentially a new biomarker predictive of secondary non-response to csDMARDs in RA, although our findings should be validated externally and in a larger cohort.