title: Serum immune responses predict rapid disease progression among children with Crohn's disease: immune responses predict disease progression.
abstract: OBJECTIVE
  Crohn's disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients.
  
  
  METHODS
  Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated.
  
  
  RESULTS
  Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5-80.4); p = 0.03). Pediatric CD patients positive for > or =1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03).
  
  
  CONCLUSIONS
  The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.
authors.affiliation: Department of Pediatrics, Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Marla C
authors.initials: MC
authors.lastname: Dubinsky
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Lin
authors.forename: Debra
authors.initials: D
authors.lastname: Dutridge
authors.forename: Yoana
authors.initials: Y
authors.lastname: Picornell
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Landers
authors.forename: Sharmayne
authors.initials: S
authors.lastname: Farrior
authors.forename: Iwona
authors.initials: I
authors.lastname: Wrobel
authors.forename: Antonio
authors.initials: A
authors.lastname: Quiros
authors.forename: Eric A
authors.initials: EA
authors.lastname: Vasiliauskas
authors.forename: Bruce
authors.initials: B
authors.lastname: Grill
authors.forename: David
authors.initials: D
authors.lastname: Israel
authors.forename: Ron
authors.initials: R
authors.lastname: Bahar
authors.forename: Dennis
authors.initials: D
authors.lastname: Christie
authors.forename: Ghassan
authors.initials: G
authors.lastname: Wahbeh
authors.forename: Gary
authors.initials: G
authors.lastname: Silber
authors.forename: Saied
authors.initials: S
authors.lastname: Dallazadeh
authors.forename: Praful
authors.initials: P
authors.lastname: Shah
authors.forename: Danny
authors.initials: D
authors.lastname: Thomas
authors.forename: Drew
authors.initials: D
authors.lastname: Kelts
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hershberg
authors.forename: Charles O
authors.initials: CO
authors.lastname: Elson
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Huiying
authors.initials: H
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003113:Colonoscopy; D003424:Crohn Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005408:Flagellin / Q000097:blood / Q000276:immunology*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010641:Phenotype; D018272:Porins / Q000097:blood / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000097:blood / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers; C502160:CBir1 flagellin; C113724:OmpC protein; D018272:Porins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D005408:Flagellin