Familial expression of anti-Escherichia coli outer membrane porin C in relatives of patients with Crohn's disease.
OBJECTIVE
Crohn's disease (CD) is a genetically complex disorder with strong familial aggregation. Pathogenesis appears to involve dysregulation of the immune response to endogenous bacteria. Anti-Escherichia coli outer membrane porin C (anti-OmpC) expression reflects an exaggerated response to commensal bacteria and occurs with higher frequency in CD. The aim of this study was to determine whether there is familial aggregation and genetic determination of anti-OmpC expression in CD families.


METHODS
Study groups consisted of 787 CD patients, 389 ulcerative colitis (UC) patients, 619 unaffected relatives, and 216 healthy controls. Serum anti-OmpC was detected by enzyme-linked immunosorbent assay.


RESULTS
CD patients had a greater percentage of anti-OmpC than UC patients and healthy controls. Anti-OmpC expression was more frequent in unaffected relatives from CD-only or mixed families, compared with healthy controls (P = .002 and .0001, respectively), and it was more frequent in UC patients from mixed families than those from UC-only families (P = .02). There was a significant familiality in anti-OmpC expression: P = .02 for qualitative concordance and P < .0001 for quantitative intraclass correlation. The heritability estimate for anti-OmpC level was .39 (P < .0001).


CONCLUSIONS
Anti-OmpC is a heritable immunophenotype. Increased anti-OmpC expression in the unaffected family members of CD patients suggests that anti-OmpC may be an immunologic risk marker for CD. That UC patients in mixed families had a higher response to OmpC than those in UC-only families indicates pathophysiologic heterogeneity within UC.
Mei
Ling
L
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Targan
Stephan R
SR
Landers
Carol J
CJ
Dutridge
Debra
D
Ippoliti
Andrew
A
Vasiliauskas
Eric A
EA
Papadakis
Konstantinos A
KA
Fleshner
Phillip R
PR
Rotter
Jerome I
JI
Yang
Huiying
H
D000906:Antibodies / Q000097:blood*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology; D005190:Family; D006801:Humans; D018272:Porins / Q000276:immunology*; D035781:Siblings
D000906:Antibodies; C113724:OmpC protein; D018272:Porins