Lampros Fotis1,2, Nurmohammad Shaikh1,2, Kevin W Baszis1,2, Charles M Samson1,2, Raffi Lev-Tzion1,2, Anthony R French1,2, Phillip I Tarr3,4. 1. From the Divisions of Rheumatology and Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA; Nottingham University Hospitals, UK National Health Service (NHS) Trust, Nottingham, UK; Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel. 2. L. Fotis, MD, PhD, Consultant Pediatric Rheumatologist, Nottingham University Hospitals; N. Shaikh, PhD, Staff Scientist, Department of Pediatrics, Washington University in St. Louis; K.W. Baszis, MD, Assistant Professor of Pediatrics, Pediatric Rheumatology, Washington University in St. Louis; C.M. Samson, MD, Assistant Professor of Pediatrics, Pediatric Gastroenterology, Washington University in St. Louis; R. Lev-Tzion, MD, Assistant Professor, Pediatric Gastroenterology, Shaare Zedek Medical Center; A.R. French, MD, PhD, Associate Professor of Pediatrics, Pediatric Rheumatology, Washington University in St. Louis; P.I. Tarr, MD, Professor of Pediatrics, Pediatric Gastroenterology, Washington University in St. Louis. 3. From the Divisions of Rheumatology and Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA; Nottingham University Hospitals, UK National Health Service (NHS) Trust, Nottingham, UK; Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel. tarr@kids.wustl.edu french_a@kids.wustl.edu. 4. L. Fotis, MD, PhD, Consultant Pediatric Rheumatologist, Nottingham University Hospitals; N. Shaikh, PhD, Staff Scientist, Department of Pediatrics, Washington University in St. Louis; K.W. Baszis, MD, Assistant Professor of Pediatrics, Pediatric Rheumatology, Washington University in St. Louis; C.M. Samson, MD, Assistant Professor of Pediatrics, Pediatric Gastroenterology, Washington University in St. Louis; R. Lev-Tzion, MD, Assistant Professor, Pediatric Gastroenterology, Shaare Zedek Medical Center; A.R. French, MD, PhD, Associate Professor of Pediatrics, Pediatric Rheumatology, Washington University in St. Louis; P.I. Tarr, MD, Professor of Pediatrics, Pediatric Gastroenterology, Washington University in St. Louis. tarr@kids.wustl.edu french_a@kids.wustl.edu.
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.
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.
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