Serum immune responses predict rapid disease progression among children with Crohn's disease: immune responses predict disease progression.
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.
Dubinsky
Marla C
MC
Department of Pediatrics, Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Lin
Ying-Chao
YC
Dutridge
Debra
D
Picornell
Yoana
Y
Landers
Carol J
CJ
Farrior
Sharmayne
S
Wrobel
Iwona
I
Quiros
Antonio
A
Vasiliauskas
Eric A
EA
Grill
Bruce
B
Israel
David
D
Bahar
Ron
R
Christie
Dennis
D
Wahbeh
Ghassan
G
Silber
Gary
G
Dallazadeh
Saied
S
Shah
Praful
P
Thomas
Danny
D
Kelts
Drew
D
Hershberg
Robert M
RM
Elson
Charles O
CO
Targan
Stephan R
SR
Taylor
Kent D
KD
Rotter
Jerome I
JI
Yang
Huiying
H
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*
D000907:Antibodies, Bacterial; D015415:Biomarkers; C502160:CBir1 flagellin; C113724:OmpC protein; D018272:Porins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D005408:Flagellin