Background: Patients with inflammatory bowel disease have higher proportions of immunoglobulin G (IgG) antibodies lacking N-galactose, also called agalactosyl IgG, in their serum. Such agalactosyl IgGs have been associated with disease activity and the immunogenicity of biologics. The aim was to describe the relationship between circulating levels of a subset of agalactosyl IgGs (anti-α-Gal) and Crohn's disease (CD) phenotypes.
Methods: Prospectively collected serum samples of a well-characterized cohort of patients with inflammatory bowel disease and controls were used. Serum anti-α-Gal levels were measured by a high-affinity enzyme-linked immunosorbent assay and referenced to a standard control.
Results: Serum samples from 167 subjects were tested; 62 with CD, 76 with ulcerative colitis, and 29 controls. Agalactosyl anti-α-Gal levels were significantly higher in active CD than in active ulcerative colitis (P = 0.0043) or healthy controls (P < 0.0001). Among patients with CD, agalactosyl anti-α-Gal levels were significantly higher in those with a history of arthritis, than those without (P = 0.0002), but lower in those taking immunomodulators (P = 0.03). There was no correlation between agalactosyl anti-α-Gal levels and indices of Crohn's severity, including C-reactive protein levels or Harvey–Bradshaw index. Patients who were primary or secondary nonresponders to infliximab had similar agalactosyl anti-α-Gal levels to clinical responders.
Conclusions: Patients with CD have greater amounts of agalactosylated anti-α-Gal antibodies in their serum, particularly in those with associated joint disease. This increase seems to be independent of indices of disease activity, but is influenced by immunomodulator use.
Article first published online 31 October 2013
*Liver Disease Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts;
†Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and
‡Department of Microbiology and Immunology, Drexel College of Medicine, Pennsylvania Biotechnology Center, Philadelphia, Pennsylvania.
Reprints: Alan C. Moss, MD, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (e-mail: firstname.lastname@example.org).
The authors have no conflicts of interest to disclose.
P. Safaie and M. Ham equally contributed to this work.
A.S. Mehta, M. Wang, and T.M. Block were supported by grants NCI CA136607 and CA168856-01 from the National Cancer Institute (NCI), the Hepatitis B Foundation, and an appropriation from the Commonwealth of Pennsylvania. A.C. Moss was supported by NIH grant K23DK084338.
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Received August 27, 2013
Accepted September 6, 2013