Antibodies to CBir1 Are Associated With Glycogen Storage Disease Type Ib

ABSTRACT Objectives: Glycogen storage disease (GSD) type Ib is a congenital disorder of glycogen metabolism that is associated with neutropenia, neutrophil and monocyte dysfunction, and an inflammatory bowel disease (IBD) that mimics a Crohn disease phenotype. The enteric microflora is implicated in the pathogenesis of IBD; however, its role in the development of GSD‐associated IBD is unknown. Antibody reactivity to Saccharomyces cerevisiae antibodies (ASCA), Escherichia coli outer membrane porin C (anti‐OmpC), and bacterial flagellin (anti‐CBir1) have been associated with Crohn disease in the general population, but they have an undetermined association in children and adults with GSD‐Ib. Our goal was to examine the association of ASCA, anti‐OmpC, and anti‐CBir1 with the clinical features of GSD‐Ib enterocolitis. Patients and Methods: A retrospective review identified 19 patients with GSD‐Ib with or without a known diagnosis of enterocolitis. Radiographic, endoscopic, and serologic data were collected and assays for ASCA, anti‐OmpC, and anti‐CBir1 obtained. Results: Seven patients had combined radiographic, endoscopic, and histologic evidence of intestinal inflammation; the majority had ileocolonic involvement. Seventeen of 19 (89%) patients had elevated anti‐CBir1 levels (6/7 in the IBD group and 11/12 in the no clinical evidence of IBD group). Thirteen of 19 (68%) had elevated anti‐OmpC levels (5/7 in the IBD group and 8/12 in the no clinical evidence of IBD group). Eleven of 19 (58%) patients had elevated ASCA IgA levels (4/7 in the IBD group and 7/12 in the no clinical evidence of IBD group). Conclusions: Nearly all of the patients with GSD‐Ib had elevated anti‐CBir1 levels. The antibody did not differentiate those with and without a diagnosis of GSD‐Ib‐associated IBD. Seroreactivity to flagellin may represent immune dysfunction rather than active enterocolitis in this patient population. Long‐term follow‐up of the group without known IBD is required to determine whether these antibodies can predict intestinal inflammation.