Anti-Proteinase 3 Antibodies as a Biomarker for Ulcerative Colitis and Primary Sclerosing Cholangitis in Children

Objectives: Anti-neutrophil cytoplasmic antibody (ANCA) directed against proteinase 3 (PR3) is a marker for granulomatosis with polyangiitis, but is also found in patients with inflammatory bowel disease (IBD), mainly ulcerative colitis (UC). The aim of our study was to investigate ANCA and PR3-ANCA in paediatric IBD. Methods: We tested 326 paediatric IBD patients and 164 controls for anti-Saccharomyces cerevisiae antibodies (ASCA), ANCA (indirect immunofluorescence, IIF) and PR3-ANCA (chemiluminescence immunoassay). We applied the Paris classification for paediatric IBD and documented liver manifestations such as primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Results: We found PR3-ANCA in 49/121 (40%) of UC, 20/187 (11%) of Crohn disease (CD) and 2/18 (11%) of IBD-unclassified (IBD-U) patients but in none of the controls. 54% UC and 12% CD patients were positive for ANCA (IIF). PR3-ANCA positive UC patients were characterised by more extensive disease (P = .070). Fourteen of 21 (67%) of UC patients with backwash ileitis were anti-PR3 ANCA-positive (P = .011). We diagnosed PSC or PSC/AIH in 19 UC and 3 IBD-U patients. Fifteen of 22 (68%) patients with PSC or PSC/AIH were anti-PR3-ANCA positive in contrast to 36 of 117 (32%) patients without PSC (P = .001). PR3-ANCA positive patients showed higher levels of gamma-glutamyl transferase, alanine transaminase and aspartate transferase (P< 0.001, 0.001, 0.006, respectively). Forty-seven percent of CD and 6% of UC patients were ASCA-IgA positive. PR3-ANCA-positive and -negative patients showed no significant differences concerning age at diagnosis, disease activity, need for drugs, and number of hospitalisations. Conclusions: Our study provides data for PR3-ANCA as a potential serological marker for paediatric UC and PSC.