A positive test for the proteinase 3-anti-neutrophil cytoplasmic antibodies (PR3-ANCA) may differentiate ulcerative colitis (UC) from Crohn’s disease (CD) in children and adolescents with inflammatory bowel disease (IBD), a study suggests.
The study, “PR3-ANCA and panel diagnostics in pediatric inflammatory bowel disease to distinguish ulcerative colitis from Crohn’s disease,” was published in the journal PLOS ONE.
Establishing a correct IBD diagnosis can be challenging due to atypical presentations of both CD and UC, which complicates disease management. According to the revised Porto criteria, antibody testing may help distinguish between CD and UC in children and adolescents, although the existence of fewer markers of UC than those of CD is a limitation.
ANCAs are one of the most investigated antibodies in IBD. They can be subdivided into specific subtypes based on distinct tissue and cell staining patterns, as assessed by a technique called immunofluorescence. PR3-ANCA is a hallmark of granulomatosis with polyangiitis, a subset of ANCA-associated vasculitis (AAV). It has also been associated with UC in adults, including a link to more extended disease.
In this study, researchers from the University Children’s Hospital Bern and the Children’s Hospital Lucerne, in Switzerland, explored PR3-ANCA testing as a tool for UC diagnosis in children and adolescents with IBD.
The investigators also conducted an extensive antibody profiling to obtain an optimal antibody panel to differentiate CD and UC. For this purpose, they determined the prevalence of PR3-ANCA; myeloperoxidase (MPO)-ANCA, a marker for the AAV type microscopic polyangiitis; pANCA, cANCA, and xANCA (different cell staining patterns of ANCAs); anti-Saccharomyces cerevisiae antibodies (ASCA), also thoroughly studied in IBD; pancreatic autoantibodies (PAB), previously shown at higher levels in CD patients diagnosed before 17 years of age; and autoantibodies against gastric goblet cells (gGAB), also suggested as a marker for pediatric CD patients.
In a further analysis, the team evaluated whether antibodies may predict disease phenotype (characteristics) and behavior.
A total of 61 IBD patients (32 males, with a mean age at diagnosis of 11.2 years) and 61 control individuals without IBD were included, all younger than 18 years. Of the IBD patients, 33 had UC and 28 had CD. The non-IBD participants had symptoms resembling IBD such as abdominal pain, diarrhea, rectal bleeding, and weight loss.
Collected clinical data included age at diagnosis, serum sampling, gender, body measures, disease-specific activity scores, laboratory results, extra-intestinal manifestations, medical treatment, and need for surgery during follow-up.
The median time lapse between IBD diagnosis and serum sampling was 4.3 months. Most patients had already received treatment at the time of serum sampling.
PR3-ANCA was specifically associated with UC, with a 58% sensitivity and a 93% specificity. Additionally, a four antibody-panel including PR3-ANCA, xANCA, pANCA, and ASCA IgG — the most abundant immunoglobulin class in humans — revealed significant ability to distinguish between UC and CD in two different groups of patients.
In contrast, PAB, GAB, and gGAB did not enable differentiation of IBD subtypes. None of the non-IBD controls had PR3-ANCA, pANCA, xANCA, or PAB.
Data also revealed that CD patients with ASCA IgA — a different immunoglobulin type — had a more complicated and severe disease course, while those with IgG were more likely to have with ileocolonic disease (affecting the ileum and colon). In addition, having a greater number of positive antibody responses correlated with a more complicated disease course.
“In a pediatric and adolescent cohort of IBD patients, we could show that PR3-ANCA is a strong marker for UC,” the scientists wrote, adding that the antibody panel containing PR3-ANCA “is superior” and “can support accurate classification in the work-up of pediatric and adolescent patients with IBD.”
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