Elizabeth A Spencer1, Sonia M Davis2, David R Mack3, Brendan M Boyle4, Anne M Griffiths5, Neal S LeLeiko6, Cary G Sauer7, David J Keljo8, James F Markowitz9, Susan S Baker10, Joel R Rosh11, Robert N Baldassano12, Maria Oliva-Hemker13, Marian D Pfefferkorn14, Anthony R Otley15, Melvin B Heyman16, Joshua D Noe17, Ashish S Patel18, Paul A Rufo19, M Alison Marquis2, Thomas D Walters5, Margaret H Collins20, Subra Kugathasan7, Lee A Denson20, Jeffrey S Hyams21, Marla C Dubinsky1. 1. Icahn School of Medicine, Mount Sinai Hospital, New York, New York, USA. 2. Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, North Carolina, USA. 3. Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada. 4. Nationwide Children's Hospital, Columbus, Ohio, USA. 5. University of Toronto, Toronto, Ontario, Canada. 6. Hasbro Children's Hospital, Providence, Rhode Island, USA. 7. Emory University, Atlanta, Georgia, USA. 8. Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA. 9. Northwell Health, New York, New York, USA. 10. University of Buffalo, Buffalo, New York, USA. 11. Goryeb Children's Hospital, Morristown, New Jersey, USA. 12. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 13. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 14. Riley Children's, Indiana University, Carmel, Indiana, USA. 15. Dalhousie University, Halifax, Nova Scotia, Canada. 16. University of California at San Francisco, San Francisco, California, USA. 17. Medical College of Wisconsin, Milwaukee, Wisconsin, USA. 18. UT Southwestern, Dallas, Texas, USA. 19. Boston Children's Hospital, Boston, Massachusetts, USA. 20. Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 21. Connecticut Children's Medical Center, Hartford, Connecticut, USA.
Abstract
Background: In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim: The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods: Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results: Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions: The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.
Background: In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim: The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods:Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results: Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions: The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.
Authors: J Hyams; P Davis; T Lerer; R B Colletti; A Bousvaros; A Leichtner; K Benkov; C Justinich; J Markowitz Journal: J Pediatr Gastroenterol Nutr Date: 1997-08 Impact factor: 2.839
Authors: James Markowitz; Subra Kugathasan; Marla Dubinsky; Ling Mei; Wallace Crandall; Neal LeLeiko; Maria Oliva-Hemker; Joel Rosh; Jonathan Evans; David Mack; Anthony Otley; Marian Pfefferkorn; Ron Bahar; Eric Vasiliauskas; Ghassan Wahbeh; Gary Silber; J Antonio Quiros; Iwona Wrobel; Justin Nebel; Carol Landers; Yoanna Picornell; Stephan Targan; Trudy Lerer; Jeffrey Hyams Journal: Inflamm Bowel Dis Date: 2009-05 Impact factor: 5.325
Authors: Jeffrey Hyams; James Markowitz; Trudy Lerer; Anne Griffiths; David Mack; Athos Bousvaros; Anthony Otley; Jonathan Evans; Mariann Pfefferkorn; Joel Rosh; Robert Rothbaum; Subra Kugathasan; Adam Mezoff; Robert Wyllie; Vasundhara Tolia; J Fernando delRosario; M Susan Moyer; Maria Oliva-Hemker; Neal Leleiko Journal: Clin Gastroenterol Hepatol Date: 2006-07-03 Impact factor: 11.382
Authors: Brendan Boyle; Margaret H Collins; Zhu Wang; David Mack; Anne Griffiths; Cary Sauer; James Markowitz; Neal LeLeiko; David Keljo; Joel Rosh; Susan S Baker; Marian Pfefferkorn; Melvin Heyman; Ashish Patel; Robert Baldassano; Joshua Noe; Paul Rufo; Subra Kugathasan; Thomas Walters; Lee Denson; Jeffrey Hyams Journal: Am J Surg Pathol Date: 2017-11 Impact factor: 6.394
Authors: Jodie Ouahed; Elizabeth Spencer; Daniel Kotlarz; Dror S Shouval; Matthew Kowalik; Kaiyue Peng; Michael Field; Leslie Grushkin-Lerner; Sung-Yun Pai; Athos Bousvaros; Judy Cho; Carmen Argmann; Eric Schadt; Dermot P B Mcgovern; Michal Mokry; Edward Nieuwenhuis; Hans Clevers; Fiona Powrie; Holm Uhlig; Christoph Klein; Aleixo Muise; Marla Dubinsky; Scott B Snapper Journal: Inflamm Bowel Dis Date: 2020-05-12 Impact factor: 5.325