Background: Antineutrophil cytoplasmic antibodies (ANCA) are antibodies directed against cytoplasmic antigens localized in granules of neutrophils and monocytes which play a crucial role in the pathogenesis of ulcerative colitis (UC). In this study, we evaluated whether ANCA is a useful serologic-biomarker in the clinical course of UC patients.
Methods: 58 UC patients, in whom proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA were evaluated at Kitano hospital from October 2007 to June 2016, were analyzed, retrospectively. Clinical and endoscopic activities were evaluated with Lichtiger index and Mayo score, respectively. The positivity of PR3-ANCA and MPO-ANCA were defined to be more than a titer of 1.0 (U/ml). Clinical remission (CR) was defined as less than 5 points of Lichtiger index, and endoscopic mucosal healing (MH) was defined as Mayo-0 or 1, respectively. We analyzed the ratio of positive for PR3- and MPO-ANCA in UC patients, and also evaluated the differences of clinical-features and –course of UC between ANCA-positive and -negative group.
Results: Out of 58 UC-patients, 37 (63.8%) and 6 (10.3%) were positive for PR3-ANCA and MPO-ANCA, respectively. All the patients positive for MPO-ANCA were also positive for PR3-ANCA.
The ratio of patients with extensive or left-sided colitis in the PR3-ANCA-positive group was significantly higher than that in the PR3-ANCA-negative group (97.3% and 66.7%, respectively; p<0.01). On the other hand, there was no significant difference in clinical characteristics at evaluating ANCA, such as Lichtiger index, serum level of C-reactive protein (CRP) and albumin between the PR3-ANCA-positive group and -negative group.
However, regression analysis demonstrated that the titer of PR3-ANCA was significantly related with the serum level of albumin at evaluating ANCA (r=0.54, p<0.01), although there was no significant relationship between the titer of PR3-ANCA and clinical-markers, such as Lichtiger index (p=0.59), and the serum CRP level (p=0.08).
The ratio of patients with history of intensive therapies such as immunomodulators (IM) and anti-tumor necrosis factor (TNF)-alpha agents in the PR3-ANCA-positive group was significantly higher than that in the PR3-ANCA-negative group (IM; 56.8% and 23.8%, respectively; p=0.03, anti-TNF-alpha agents; 37.8% and 4.8%, respectively; p<0.01).
In the subsequent clinical course, the ratio of UC-patients requiring surgery in the PR3-ANCA-positive group was also high compared with the PR3-ANCA-negative group, although there was no significance (10.8% and 4.8%, respectively; p=0.64).
Conclusions: Our data suggested that PR3-ANCA might be a useful serum biomarker for predicting the refractoriness of UC.