Serum acetate and lipopolysaccharide levels correlate with disease activity in patients with lupus nephritis

Abstract

BACKGROUND: Lupus nephritis is a severe manifestation of systemic lupus erythematosus and is associated with poor prognosis. The gut microbiota has been implicated in the etiology of autoimmune diseases. Bacterial products from the gut may enter the circulation and induce inflammatory responses. Acetate is a short chain fatty acid (SCFA) produced by gut microbiota and lipopolysaccharide (LPS) is a component of the outer wall of Gram-negative bacteria. We measured serum acetate and LPS levels and intra-renal expression of their cell surface receptors in lupus nephritis patients to investigate the potential relationship between gut microbiota and lupus nephritis pathogenesis. METHODS: Serum acetate and LPS levels were measured in patients with biopsy-proven severe proliferative lupus nephritis, patients with non-lupus glomerular diseases and healthy controls (n=50 for each group). Intra-renal expression of LPS-binding protein (LBP) and GPR-41 and GPR-43 (SCFA receptors) was also examined. RESULTS: Serum acetate and LPS levels were significantly higher in patients with lupus nephritis compared to levels in patients with non-lupus renal diseases (P < 0.01, for both). In lupus nephritis patients, serum acetate and LPS levels were significantly higher during disease flare (P=0.04 and P=0.0015 respectively compared to levels during remission). Serum LPS level correlated with acetate level (r=0.52, P < 0.001), and inversely correlated with that of IgG (r=-0.61, P < 0.01). Renal LBP, GPR- 41 and GPR-43 expression was markedly increased in lupus nephritis patients compared to healthy controls, and was predominantly detected in the tubulo-interstitium, associated with inflammatory cell infiltration, fibrosis and tubular atrophy. LBP, GPR-41 and GPR- 43 expression showed similar staining intensities and localization in patients with lupus nephritis and those with non-lupus renal diseases. CONCLUSIONS: Our data suggest that acetate and LPS may be involved in the pathogenesis of lupus nephritis and non-lupus glomerular diseases. FUNDING: Government Support - Non-U.S.