Serologic Evidence of Gut-driven Systemic Inflammation in Juvenile Idiopathic Arthritis

Abstract

Objective: Accumulating evidence links juvenile idiopathic arthritis (JIA) to nonhost factors such as gut microbes. We hypothesize that children with new-onset JIA have increased intestinal bacterial translocation and circulating lipopolysaccharide (LPS).

Methods: We studied systemic treatment-naive patients with JIA [polyarticular JIA, n = 22, oligoarticular JIA, n = 31, and spondyloarthropathies (SpA), n = 16], patients with established inflammatory bowel disease-related arthritis (IBD-RA, n = 11), and 34 healthy controls. We determined circulating IgG reactivity against LPS, LPS-binding protein (LBP), α-1-acid glycoprotein (α-1AGP), and C-reactive protein (CRP) in plasma or serum from these patients and controls. Juvenile Arthritis Disease Activity Score (JADAS-27) was calculated for patients with JIA.

Results: Circulating anticore LPS antibody concentrations in patients with polyarticular JIA (p = 0.001), oligoarticular JIA (p = 0.024), and SpA (p = 0.001) were significantly greater than in controls, but there were no significant intergroup differences. Circulating LBP concentrations were also significantly greater in patients with polyarticular JIA (p = 0.001), oligoarticular JIA (p = 0.002), and SpA (p = 0.006) than controls, as were α-1AGP concentrations (p = 0.001, 0.001, and 0.003, respectively). No differences were observed between controls and patients with IBD-RA in any of the assays. Circulating concentrations of LBP and α-1AGP correlated strongly with CRP concentrations (r = 0.78 and r = 0.66, respectively). Anticore LPS antibody levels and CRP (r = 0.26), LBP (r = 0.24), and α-AGP (r = 0.22) concentrations had weaker correlations. JADAS-27 scores correlated with LBP (r = 0.66) and α-1AGP concentrations (r = 0.58).

Conclusion: Children with polyarticular JIA, oligoarticular JIA, and SpA have evidence of increased exposure to gut bacterial products. These data reinforce the concept that the intestine is a source of immune stimulation in JIA.

Keywords: ACUTE-PHASE PROTEINS; INTESTINAL PERMEABILITY; JUVENILE IDIOPATHIC ARTHRITIS; LIPOPOLYSACCHARIDE; LIPOPOLYSACCHARIDE-BINDING PROTEIN; α1-ACID GLYCOPROTEIN.

Figure 1

Circulating anti-core LPS antibody concentrations across groups. *Outliers above Q3 + 1.5 IQR, °Outliers between Q3 and Q3 + 1.5 IQR IQR (interquartile range)

Figure 2

Circulating LBP concentrations across groups. Outliers between Q3 and Q3 + 1.5 IQR IQR (interquartile range)

Figure 3

Circulating A1AGP concentrations across groups. Outliers between Q3 and Q3 + 1.5 IQR IQR (interquartile range)