title: Increased immune reactivity predicts aggressive complicating Crohn's disease in children.
abstract: OBJECTIVE
  The ability to identify children with CD who are at highest risk for rapid progression from uncomplicated to complicated phenotypes would be invaluable in guiding initial therapy. The aims of this study were to determine whether immune responses and/or CARD15 variants are associated with complicated disease phenotypes and predict disease progression.
  
  
  METHODS
  Sera were collected from 796 pediatric CD cases and tested for anti-Cbir1 (flagellin), anti-outer membrane protein C, anti-Saccharomyces cerevisiae, and perinuclear antineutrophil cytoplasmic antibody by using enzyme-linked immunosorbent assay. Genotyping (Taqman MGB) was performed for 3 CARD15 variants (single nucleotide polymorphisms 8, 12, and 13). Associations between immune responses (antibody sum and quartile sum score, CARD15, and clinical phenotype were evaluated.
  
  
  RESULTS
  Thirty-two percent of patients developed at least 1 disease complication within a median of 32 months, and 18% underwent surgery. The frequency of internal penetrating, stricturing, and surgery significantly increased (P trend < .0001 for all 3 outcomes) with increasing antibody sum and quartile sum score. Nine percent of seropositive groups had internal penetrating/stricturing versus 2.9% in the seronegative group (P = .01). Twelve percent of seropositive groups underwent surgery versus 2% in the seronegative group (P = .0001). The highest antibody sum group (3) and quartile sum score group (4) demonstrated the most rapid disease progression (P < .0001). Increased hazard ratio was observed for antibody sum group 3 (7.8; confidence interval, 2.2-28.7), P < .002 and quartile sum score group 4 (11.0; confidence interval, 1.5-83.0, P < .02).
  
  
  CONCLUSIONS
  The rate of complicated CD increases in children as the number and magnitude of immune reactivity increase. Disease progression is significantly faster in children expressing immune reactivity.
authors.affiliation: Department of Pediatrics, IBD Center, Cedars Sinai Medical Center, Los Angeles, California, USA. dubinskym@csmc.edu
authors.forename: Marla C
authors.initials: MC
authors.lastname: Dubinsky
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
authors.forename: Ling
authors.initials: L
authors.lastname: Mei
authors.forename: Yoana
authors.initials: Y
authors.lastname: Picornell
authors.forename: Justin
authors.initials: J
authors.lastname: Nebel
authors.forename: Iwona
authors.initials: I
authors.lastname: Wrobel
authors.forename: Antonio
authors.initials: A
authors.lastname: Quiros
authors.forename: Gary
authors.initials: G
authors.lastname: Silber
authors.forename: Ghassan
authors.initials: G
authors.lastname: Wahbeh
authors.forename: Lirona
authors.initials: L
authors.lastname: Katzir
authors.forename: Eric
authors.initials: E
authors.lastname: Vasiliauskas
authors.forename: Ron
authors.initials: R
authors.lastname: Bahar
authors.forename: Anthony
authors.initials: A
authors.lastname: Otley
authors.forename: David
authors.initials: D
authors.lastname: Mack
authors.forename: Jonathan
authors.initials: J
authors.lastname: Evans
authors.forename: Joel
authors.initials: J
authors.lastname: Rosh
authors.forename: Maria Oliva
authors.initials: MO
authors.lastname: Hemker
authors.forename: Neal
authors.initials: N
authors.lastname: Leleiko
authors.forename: Wallace
authors.initials: W
authors.lastname: Crandall
authors.forename: Christine
authors.initials: C
authors.lastname: Langton
authors.forename: Carol
authors.initials: C
authors.lastname: Landers
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: James
authors.initials: J
authors.lastname: Markowitz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hyams
mesh_terms: D000293:Adolescent; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000907:Antibodies, Bacterial / Q000097:blood; D000908:Antibodies, Fungal / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000175:diagnosis* / Q000276:immunology* / Q000601:surgery; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005408:Flagellin / Q000276:immunology; D005838:Genotype; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007223:Infant; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D011110:Polymorphism, Genetic; D011379:Prognosis; D012441:Saccharomyces cerevisiae / Q000276:immunology; D013223:Statistics as Topic
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000907:Antibodies, Bacterial; D000908:Antibodies, Fungal; C502160:CBir1 flagellin; D053473:Nod2 Signaling Adaptor Protein; D005408:Flagellin