TY - JOUR
T1 - Serologic evidence of gut-driven systemic inflammation in juvenile idiopathic arthritis
AU - Fotis, Lampros
AU - Shaikh, Nurmohammad
AU - Baszis, Kevin W.
AU - Samson, Charles M.
AU - Lev-Tzion, Raffi
AU - French, Anthony R.
AU - Tarr, Phillip I.
N1 - Funding Information:
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. Supported by US National Institutes of Health Grants P30DK052574 (DDRCC Biobank Core), UL1TR000448, and P30CA091842 (for REDCap), and funding from the Melvin E. Carnahan Professorship (Dr. Tarr). 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. Address correspondence to Dr. P.I. Tarr, Department of Pediatrics, Washington University, Box 8208, 660 South Euclid Ave., St. Louis, Missouri 63110, USA, E-mail: tarr@kids.wustl.edu; or Dr. A.R. French, Department of Pediatrics, Washington University, Box 8208, 660 South Euclid Ave., St. Louis, Missouri 63110, USA. E-mail: french_a@kids.wustl.edu Accepted for publication June 21, 2017.
Publisher Copyright:
Copyright © 2017. All rights reserved.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - Acute-phase proteins α1-acid glycoprotein
KW - Intestinal permeability
KW - Juvenile idiopathic arthritis
KW - Lipopolysaccharide lipopolysaccharide-binding protein
UR - http://www.scopus.com/inward/record.url?scp=85032628883&partnerID=8YFLogxK
U2 - 10.3899/jrheum.161589
DO - 10.3899/jrheum.161589
M3 - Article
C2 - 28916545
AN - SCOPUS:85032628883
SN - 0315-162X
VL - 44
SP - 1624
EP - 1631
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 11
ER -