Anti-neutrophil cytoplasmic antibodies (ANCA) specific for one or several antigens: useful markers for subtypes of ulcerative colitis and associated primary sclerosing cholangitis

Background: Dysregulation of antimicrobial response may trigger inflammatory bowel diseases (IBD). This study analyzed specificity of anti-neutrophil cytoplasmic antibodies (ANCA) in IBD patients and its clinical significance. Methods: Data from 52 ulcerative colitis (UC) patients with 32 Crohn's disease (CD) patients were compared. Primary sclerosing cholangitis (PSC) was present in 12/84 patients. ANCA, ANA and anti-smooth muscle antibodies (ASMA) were detected by IIF. ANCA were tested by ELISA for proteinase; 3 (PR3), myeloperoxidase, bactericidal/permeability increasing protein, elastase, cathepsin G, lysozyme and lactoferrin. Results: pANCA were more frequently present in UC than in CD patients (p<0.001). ANCA titer correlated with the disease activity only in UC patients (p<0.05). UC patients more frequently had two or more ANCA specificities compared to CC patients (p<0.01). Multi-specific ANCA in medium and/or high concentrations were associated with long-lasting (p<0.05) and left-sided UC (p<0.001). Multi-specific ANCA with ANA and ASMA had sensitivity of 67% for PSC. Conclusions: Higher concentrations of multi-specific ANCA in long-lasting, left-sided UC suggest an influence of bacterial stimulation on the break of tolerance. Multi-specific ANCA with ANA and ASMA could be markers for PSC. ANCA specific to several antigens may worsen inflammation by reducing antimicrobial capacity of neutrophil proteases and cationic proteins.