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J Rheumatol. 2017 Nov;44(11):1624-1631. doi: 10.3899/jrheum.161589. Epub 2017 Sep 15.

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

Author information

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.

KEYWORDS:

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

PMID:
28916545
PMCID:
PMC5904838
DOI:
10.3899/jrheum.161589
[Indexed for MEDLINE]
Free PMC Article

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