Age of diagnosis influences serologic responses in children with Crohn's disease: a possible clue to etiology?
BACKGROUND
Crohn's disease (CD) is often associated with antibodies to microbial antigens. Differences in immune response may offer clues to the pathogenesis of the disease. The aim was to examine the influence of age at diagnosis on the serologic response in children with CD.


METHODS
Data were drawn from 3 North American multicenter pediatric inflammatory bowel disease (IBD) research consortia. At or shortly after diagnosis, pANCA, ASCA IgA, ASCA IgG, anti-ompC, and anti-CBir1 were assayed. The results were compared as a function of age at CD diagnosis (0-7 years versus 8-15 years).


RESULTS
In all, 705 children (79 <8 years of age at diagnosis, 626 >or=8 years) were studied. Small bowel CD was less frequent in the younger group (48.7% versus 72.6%; P < 0.0001), while colonic involvement was comparable (91.0% versus 86.5%). ASCA IgA and IgG were seen in <20% of those 0-7 years old compared to nearly 40% of those 8-15 years old (P < 0.001), while anti-CBir1 was more frequent in the younger children (66% versus 54%, P < 0.05). Anti-CBir1 detected a significant number of children in both age groups who otherwise were serologically negative. Both age at diagnosis and site of CD involvement were independently associated with expression of ASCA and anti-CBir1.


CONCLUSIONS
Compared to children 8-15 years of age at diagnosis, those 0-7 years are more likely to express anti-CBir1 but only half as likely to express ASCA. These age-associated differences in antimicrobial seropositivity suggest that there may be different, and as yet unrecognized, genetic, immunologic, and/or microbial factors leading to CD in the youngest children.
Markowitz
James
J
Division of Pediatric Gastroenterology, North Shore, LIJ Health System, New Hyde Park, New York, USA. jmarkowi@nshs.edu
Kugathasan
Subra
S
Dubinsky
Marla
M
Mei
Ling
L
Crandall
Wallace
W
LeLeiko
Neal
N
Oliva-Hemker
Maria
M
Rosh
Joel
J
Evans
Jonathan
J
Mack
David
D
Otley
Anthony
A
Pfefferkorn
Marian
M
Bahar
Ron
R
Vasiliauskas
Eric
E
Wahbeh
Ghassan
G
Silber
Gary
G
Quiros
J Antonio
JA
Wrobel
Iwona
I
Nebel
Justin
J
Landers
Carol
C
Picornell
Yoanna
Y
Targan
Stephan
S
Lerer
Trudy
T
Hyams
Jeffrey
J
D000293:Adolescent; D000367:Age Factors; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000097:blood* / Q000209:etiology; D005260:Female; D005408:Flagellin / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D018272:Porins / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies
D019268:Antibodies, Antineutrophil Cytoplasmic; C502160:CBir1 flagellin; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C113724:OmpC protein; D018272:Porins; D005408:Flagellin