Serum Lipopolysaccharide, Lipopolysaccharide Binding Protein, and CD14 Levels Correlate with Disease Activity in Patients with Lupus Nephritis

Abstract

Introduction: Lupus nephritis is an important cause of renal failure. The gut microbiota is implicated in the pathogenesis of autoimmune diseases, but its role in lupus nephritis has not been investigated. Microbial components may enter the bloodstream and induce systemic inflammation. Lipopolysaccharide (LPS) is a component of the outer wall of Gram-negative bacteria. Through interaction with LPS binding protein (LBP) then transferral to its receptor CD14, LPS could activate immune and non-immune cells. We examined the relationship between the levels of serum LPS, LBP, and CD14 and disease parameters in lupus nephritis patients. Methods: Paired serum samples during active disease or remission from 50 patients with biopsy-proven Class III/IV±V lupus nephritis were included, and sera from patients with non-lupus renal diseases and healthy subjects served as controls. LPS, LBP, and CD14 levels were measured by commercially available limulus amebocyte lysate test and ELISA. Permeability of the intestinal mucosal in NZBWF1/J mice was investigated by dextran-FITC administration and ZO-1 expression. Results: Serum LPS and CD14 levels were significantly higher (P<0.05 for both) in lupus nephritis patients compared with other renal disease and healthy subjects (P<0.05 for both). Serum LBP level was significantly higher in lupus nephritis and non-lupus renal disease patients than in healthy subjects (P<0.05 for both). Serum LPS, LBP, and CD14 levels were higher during disease flare compared with remission in patients with lupus nephritis (P=0.016, 0.025 and 0.035 respectively). LPS level inversely correlated with IgG level (r=-0.253, P=0.029). LBP level correlated with that of anti-dsDNA antibody, CD14, IL-6, and IL-8. CD14 level correlated with that of anti-dsDNA antibody, IL-6, and IL-8, and inversely with C3 level, lymphocyte and neutrophil counts. Gut permeability was increased in NZBWF1/J mice with active nephritis, and this was associated with marked reduction in ZO-1 expression. Conclusions: The data showed that, probably consequent to increased gut permeability, microbiota products are present in the circulation of patients with active lupus nephritis and are related to pro-inflammatory biomarkers.