Both preoperative perinuclear antineutrophil cytoplasmic antibody and anti-CBir1 expression in ulcerative colitis patients influence pouchitis development after ileal pouch-anal anastomosis

Abstract

Background & aims: Acute pouchitis (AP) and chronic pouchitis (CP) are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. The aim of this study was to assess associations of preoperative perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti-CBir1 flagellin on AP or CP development.

Methods: Patients were assessed prospectively for clinically and endoscopically proven AP (antibiotic responsive) or CP (antibiotic-dependent or refractory to antibiotic therapy). Sera from 238 patients were analyzed for ANCA and anti-CBir1 using an enzyme-linked immunosorbent assay. pANCA(+) patients were substratified into high-level (>100 EU/mL) and low-level (<100 EU/mL) groups.

Results: After a median follow-up period of 47 months, 72 patients (30%) developed pouchitis. Pouchitis developed in 36% of pANCA(+) patients versus 16% of pANCA(-) patients (P = .005), 46% of anti-CBir1(+) patients versus 26% of anti-CBir1(-) patients (P = .02), and 54% of 35 pANCA(+)/anti-CBir1(+) patients versus 31% of 136 pANCA(+)/anti-CBir1(-) patients (P = .02). AP developed in 37 pANCA(+) patients (22%) versus 6 pANCA(-) patients (9%) (P = .02), and 12 anti-CBir1(+) patients (26%) versus 31 anti-CBir1(-) patients (16%) (P = .1). Although AP was not influenced by pANCA level, AP was seen in 38% of low-level pANCA(+)/anti-CBir1(+) patients versus 18% low-level pANCA(+)/anti-CBir1(-) patients (P = .03). CP was seen in 29% of high-level pANCA(+) patients versus 11% of low-level pANCA(+) patients (P = .03).

Conclusions: Both pANCA and anti-CBir1 expression are associated with pouchitis after IPAA. Anti-CBir1 increases the incidence of AP only in patients who have low-level pANCA expression, and increases the incidence of CP only in patients who have high-level pANCA expression. Diverse patterns of reactivity to microbial antigens may manifest as different forms of pouchitis after IPAA.

Figure 1

Anti-CBir1 was expressed in 19% of patients. Lines indicate the median level for each group. The percentage of positive samples defined as >2 SD above the mean of the normal controls for each group is shown.

Figure 2

Relationship between pANCA and anti-CBir1 seroreactivity and the overall incidence of pouchitis. There was a significantly higher incidence of pouchitis noted in pANCA⁺ patients versus pANCA^- patients (*p=0.005). Anti-CBir expression was also associated with overall pouchitis development (**p=0.02).

Figure 3

Association between pANCA/anti-CBir1 positivity and the incidence of pouchitis. The overall incidence of pouchitis (■) rose significantly with increased seromarker positivity (p trend=0.0003). There was also a significant direct association between acute pouchitis () development (p trend=0.007) but not chronic pouchitis () development (p trend=0.05) with increasing seromarker positivity. Zero, one or two represents number of seromarkers expressed. Patient numbers are italicized along the x axis.

Figure 4

Relationship between pANCA level and pouchitis. There was a higher incidence of chronic pouchitis is patients with high-level pANCA expression (> 100 ELISA units/ml) compared to low-level pANCA expression (*p=0.03).

Figure 5

Effect of anti-CBir1 expression and pANCA level on the cumulative incidence of acute pouchitis. The risk of developing acute pouchitis after IPAA among patients with low-level pANCA (LL-pANCA+) was significantly (p=0.04) higher in patients who were also anti-CBir1⁺ (●) versus patients who were also anti-CBir ^- (○). There was no effect of anti-CBir1 on the incidence of acute pouchitis in patients with high-level pANCA (HL-pANCA+) expression.

Figure 6

Effect of anti-CBir1 expression and pANCA level on the cumulative incidence of chronic pouchitis. The risk of developing chronic pouchitis after IPAA among patients with high-level pANCA (HL-pANCA+) was significantly (p=0.04) higher in patients who were also anti-CBir1⁺ (●) versus patients who were also anti-CBir ^- (○). There was no effect of anti-CBir1 on the incidence of chronic pouchitis in patients with low-level pANCA (LL-pANCA+) expression.