Serologic testing with ANCA, ASCA, and anti-OmpC in children and young adults with Crohn's disease and ulcerative colitis: diagnostic value and correlation with disease phenotype.
OBJECTIVE
Serologic testing is increasingly being utilized to evaluate children with suspected inflammatory bowel disease (IBD). The aim of this paper was to evaluate the sensitivity and specificity of a currently available panel involving four antibodies: deoxyribonuclease (DNase)-sensitive perinuclear antineutrophil cytoplasmic antibody (DNase-sensitive pANCA), IgA and IgG antibodies to Saccharomyces cerevisiae (IgA and IgG ASCA), and antibody to Escherichia coli outer membrane porin (anti-OmpC). We also wished to determine whether antibody levels correlated with disease activity, and whether a specific antibody pattern correlated with location and outcome of disease in children.


METHODS
We studied sera from 81 children with Crohn's disease (CD), 54 with ulcerative colitis (UC), and 63 controls. Clinical data, disease activity, and disease diagnosis were gathered at the time of serum sampling, and charts were re-reviewed at time of the study to determine long-term outcome. Enzyme-linked immunosorbent assay was utilized to determine titers of antibodies to ASCA, DNase-sensitive pANCA, and anti-OmpC; the presence of perinuclear staining for ANCA was confirmed by immunofluorescence.


RESULTS
We identified ASCA antibodies in 44% of CD patients, 0% of UC patients, and 1 control patient. DNase-sensitive pANCA antibodies were found in 70% of patients with UC, 18% of CD patients (predominantly Crohn's colitis), and 3% of controls. Anti-OmpC as an isolated assay had low sensitivity for both CD (24%) and UC (11%), and displayed a 5% false-positive rate. However, anti-OmpC did identify a small number of IBD patients not detected by the other assays. If any one or more of the four antibodies was positive, the overall sensitivity of the four antibody panel was 65% for CD and 76% for UC, with a specificity of 94%. Patients who were ASCA-positive were more likely to have disease of the ileum or ileum and right colon than patients who were ASCA-negative (58%vs 18%, p < 0.001). Patients with ASCA-positive were also more likely to require ileocecal resection (36%vs 13%, p < 0.05).


CONCLUSIONS
A currently available commercial antibody panel has good sensitivity and excellent specificity for CD and UC. The ASCA antibodies, while highly specific for CD, identify predominantly the subset of children with disease of the ileum and ascending colon who may be at increased risk of surgery.
Zholudev
Anna
A
Inflammatory Bowel Disease Center, Division of Gastroenterology and Nutrition, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Zurakowski
David
D
Young
Wes
W
Leichtner
Alan
A
Bousvaros
Athos
A
D000293:Adolescent; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000907:Antibodies, Bacterial / Q000097:blood; D000908:Antibodies, Fungal / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002648:Child; D003093:Colitis, Ulcerative / Q000175:diagnosis*; D003424:Crohn Disease / Q000175:diagnosis*; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D018272:Porins / Q000276:immunology; D011237:Predictive Value of Tests; D012441:Saccharomyces cerevisiae / Q000276:immunology; D012680:Sensitivity and Specificity
D019268:Antibodies, Antineutrophil Cytoplasmic; D000907:Antibodies, Bacterial; D000908:Antibodies, Fungal; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018272:Porins