D3.392 - Associations Between Markers Of Endotoxin-Binding Systems And Vasoactive Agents In Patients With Rheumatoid Arthritis

Intestinal permeability, endotoxemia, and dysregulation of endotoxin-binding systems may contribute to immune activation and endothelial dysfunction in Rheumatoid arthritis (RA). Vasoactive agents such as endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and angiotensin II (Ang II) play a key role in vascular homeostasis and may mediate the interaction between endotoxin exposure and inflammatory pathways.

Eighty adult patients with established RA undergoing inpatient treatment were enrolled in this study. The cohort was predominantly female (77.5%), with a mean age of 53.9 ± 11.5 years and mean disease duration of 6.5 ± 4.0 years. Patients with high disease activity (DAS28 > 5.1), pregnancy, severe comorbid cardiovascular, pulmonary, hepatic, renal, infectious, oncological, or overlapping rheumatic diseases were excluded. Plasma levels of lipopolysaccharide (LPS), lipopolysaccharide-binding protein (LBP), zonulin, bactericidal/permeability-increasing protein (BPI), soluble CD14, eNOS, VEGF, ET-1, and Ang II were measured by ELISA.

Significant correlations were identified between BPI and eNOS (rₛ = 0.66, p < 0.001), LPS and VEGF (rₛ = 0.46, p < 0.001), and LBP and zonulin (rₛ = 0.43, p < 0.001). Other endotoxin-binding markers showed weak or no associations with vasoactive agents. In multiple regression analysis, VEGF emerged as the only independent predictor of LPS levels (β = 0.43, p < 0.001), while eNOS, ET-1, and Ang II were not statistically significant. The model explained 26.5% of LPS variability (adjusted R² = 0.23).

In RA, markers of endotoxin-binding systems demonstrate selective and non-uniform associations with vasoactive mediators. The strong link between BPI and eNOS suggests interaction between innate immune defense and endothelial function, while the independent association of VEGF with LPS highlights a potential role of vascular permeability in systemic endotoxemia. These findings support the concept that endotoxin-related mechanisms and endothelial dysfunction are interconnected in RA.