PMID- 16454844
OWN - NLM
STAT- MEDLINE
DCOM- 20060316
LR  - 20220408
IS  - 0002-9270 (Print)
IS  - 1572-0241 (Electronic)
IS  - 0002-9270 (Linking)
VI  - 101
IP  - 2
DP  - 2006 Feb
TI  - Serum immune responses predict rapid disease progression among children with 
      Crohn's disease: immune responses predict disease progression.
PG  - 360-7
AB  - BACKGROUND AND AIM: 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.
FAU - Dubinsky, Marla C
AU  - Dubinsky MC
AD  - Department of Pediatrics, Genetics Institute, Cedars-Sinai Medical Center, Los 
      Angeles, California, USA.
FAU - Lin, Ying-Chao
AU  - Lin YC
FAU - Dutridge, Debra
AU  - Dutridge D
FAU - Picornell, Yoana
AU  - Picornell Y
FAU - Landers, Carol J
AU  - Landers CJ
FAU - Farrior, Sharmayne
AU  - Farrior S
FAU - Wrobel, Iwona
AU  - Wrobel I
FAU - Quiros, Antonio
AU  - Quiros A
FAU - Vasiliauskas, Eric A
AU  - Vasiliauskas EA
FAU - Grill, Bruce
AU  - Grill B
FAU - Israel, David
AU  - Israel D
FAU - Bahar, Ron
AU  - Bahar R
FAU - Christie, Dennis
AU  - Christie D
FAU - Wahbeh, Ghassan
AU  - Wahbeh G
FAU - Silber, Gary
AU  - Silber G
FAU - Dallazadeh, Saied
AU  - Dallazadeh S
FAU - Shah, Praful
AU  - Shah P
FAU - Thomas, Danny
AU  - Thomas D
FAU - Kelts, Drew
AU  - Kelts D
FAU - Hershberg, Robert M
AU  - Hershberg RM
FAU - Elson, Charles O
AU  - Elson CO
FAU - Targan, Stephan R
AU  - Targan SR
FAU - Taylor, Kent D
AU  - Taylor KD
FAU - Rotter, Jerome I
AU  - Rotter JI
FAU - Yang, Huiying
AU  - Yang H
CN  - Western Regional Pediatric IBD Research Alliance
LA  - eng
GR  - M01-RR00425/RR/NCRR NIH HHS/United States
GR  - K23 DK066248-04/DK/NIDDK NIH HHS/United States
GR  - DK 46763/DK/NIDDK NIH HHS/United States
GR  - M01 RR000425/RR/NCRR NIH HHS/United States
GR  - K23 DK066248/DK/NIDDK NIH HHS/United States
GR  - P01 DK046763/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Gastroenterol
JT  - The American journal of gastroenterology
JID - 0421030
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Biomarkers)
RN  - 0 (CBir1 flagellin)
RN  - 0 (OmpC protein)
RN  - 0 (Porins)
RN  - 0 (Silent Information Regulator Proteins, Saccharomyces cerevisiae)
RN  - 12777-81-0 (Flagellin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Bacterial/*blood/immunology
MH  - Biomarkers/blood
MH  - Child
MH  - Child, Preschool
MH  - Colonoscopy
MH  - Crohn Disease/blood/*immunology/pathology
MH  - Disease Progression
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flagellin/blood/*immunology
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Phenotype
MH  - Porins/blood/*immunology
MH  - Prognosis
MH  - Prospective Studies
MH  - Silent Information Regulator Proteins, Saccharomyces cerevisiae/blood/*immunology
PMC - PMC2259248
MID - NIHMS28370
COIS- Conflict of Interest Statement: Dr. Targan is a shareholder and co-founder of 
      Prometheus Labs. Dr. Dubinsky serves as a consultant for Prometheus Labs. Carol 
      Landers is a share holder for Prometheus Labs.
EDAT- 2006/02/04 09:00
MHDA- 2006/03/17 09:00
PMCR- 2008/03/02
CRDT- 2006/02/04 09:00
PHST- 2006/02/04 09:00 [pubmed]
PHST- 2006/03/17 09:00 [medline]
PHST- 2006/02/04 09:00 [entrez]
PHST- 2008/03/02 00:00 [pmc-release]
AID - AJG456 [pii]
AID - 10.1111/j.1572-0241.2006.00456.x [doi]
PST - ppublish
SO  - Am J Gastroenterol. 2006 Feb;101(2):360-7. doi: 10.1111/j.1572-0241.2006.00456.x.