Diagnostic utility and phenotype correlation of serum ASCA and ANCA in pediatric inflammatory bowel disease

Abstract

Background Both anti-Saccharomyces cerevisiae antibody (ASCA) and anti-neutrophil cytoplasmic antibody (ANCA) are associated with inflammatory bowel disease (IBD); however, the clinical role of these serological biomarkers in pediatric IBD has been poorly investigated. Therefore, this study aimed to evaluate the diagnostic utility and phenotypic correlation of serological biomarkers in pediatric IBD. Methods A retrospective review was performed on all pediatric subjects diagnosed with IBD between March 2004 and July 2021. Pediatric patients were recruited and classified as Crohn’s disease (CD), ulcerative colitis (UC), and IBD unclassified (IBD-U) based on the revised Porto criteria. The Paris classification was used to evaluate disease phenotypes. Laboratory markers including fecal calprotectin were also evaluated. Serum levels of ASCA IgG and IgA, anti-proteinase-3 with cytoplasmic ANCA (PR3-ANCA), and anti-myeloperoxidase with perinuclear ANCA (MPO-ANCA) using ELISA, and serum ANCA titer using immunofluorescent test were measured. Results In all, 229 pediatric patients with IBD (CD: 147, UC: 53, IBD-U: 29) were included. The ASCA IgG seropositivity was significantly different among the three groups (CD: 75.4%, UC: 17.5%, and IBD-U: 60.0%; p < 0.001) and ASCA IgA seropositivity was also significantly different among the three groups (CD: 23.8%, UC: 2.5%, and IBD-U: 20.0%; p < 0.001). Serum titers of ASCA IgG were significantly difference among the 3 IBD subgroups (CD 32.7 U/mL vs. UC 11.3 U/mL vs. IBD-U 25.30 U/mL; p < 0.001), and ASCA IgA also revealed significant difference (CD 10.2 U/mL vs. UC 6.8 U/mL vs. IBD-U 9.0 U/mL; p < 0.001). Three ANCA antibodies were positive in 1.4%, 32.1%, and 37.9% of CD, UC, and IBD-U patients, respectively (p < 0.001). Perianal disease modifier P1 revealed higher ASCA IgG titers (P1 40.0 U/mL vs. P0 29.4 U/mL, p = 0.001), while showing no differences in age, disease location, and behavior. Using optimal cutoffs determined by ROC analysis, serum IgG and IgA ASCAs showed 68.0% and 63.1% sensitivity, and 67.7% and 64.6% specificity, respectively, in distinguishing CD. Conclusions Serological biomarkers of ASCAs IgG and IgA, pANCA, and PR3-ANCA may be effective in the diagnosis and clinical evaluation of disease phenotypes in an Asian pediatric IBD cohort.