High levels of Crohn's disease-associated anti-microbial antibodies are present and independent of colitis in chronic granulomatous disease

Abstract

Chronic granulomatous disease (CGD) and inflammatory bowel disease (IBD) have overlapping gastrointestinal manifestations. Serum antibodies to intestinal microbial antigens in IBD are thought to reflect a loss of tolerance in the setting of genetically encoded innate immune defects. CGD subjects studied here, with or without colitis, had considerably higher levels of ASCA IgA, ASCA IgG, anti-OmpC, anti-I2, and anti-CBir1, but absent to low pANCA, compared to IBD-predictive cutoffs. Higher antibody levels were not associated with a history of colitis. Except for higher ASCA IgG in subjects <18 years, antibody levels were not age-dependent. In comparison, 7 HIES subjects expressed negative to low antibody levels to all of these antigens; none had colitis. Our results suggest that markedly elevated levels of antimicrobial antibodies in CGD do not correlate with a history of colitis but may reflect a specific defect in innate immunity in the face of chronic antigenic stimulation.

Figure 1. Representative colonic biopsy from a CGD patient with colitis

Section of colonic mucosa from a CGD patient with colitis demonstrating (a) architectural distortion, full-thickness lymphoplasmacytosis, and Paneth cell metaplasia (200×, H&E), (b) clusters of histiocytes with brown pigment in the lamina propria, paucity of neutrophils, and scattered eosinophils (400×, H&E), and (c) pink crystalline inclusions in pigmented histiocytes (arrows) (600×, H&E).

Figure 2. Serum antibody levels in X-linked (a) or autosomal recessive (b) CGD subjects

Antimicrobial antibodies in serum samples were measured by ELISA. Median antibody titers are represented by the black lines. Antibody cutoff levels predictive for possible IBD are represented by the grey lines. *p<0.05, **p=0.2353

Figure 3. Serum antibody levels in HIES subjects

Antimicrobial antibodies in serum samples were measured by ELISA. Median antibody titers are represented by the black lines. Antibody cutoff levels predictive for possible IBD are represented by the grey lines. *p=NS