Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jan;138(1):14-22.
doi: 10.1016/j.clim.2010.08.003. Epub 2010 Oct 16.

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

Joyce E Yu  1 , Suk See De Ravin, Gulbu Uzel, Carol Landers, Stephan Targan, Harry L Malech, Steven M Holland, Wenqing Cao, Noam Harpaz, Lloyd Mayer, Charlotte Cunningham-Rundles
Affiliations

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

Joyce E Yu et al. Clin Immunol. 2011 Jan.

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.

PubMed Disclaimer

Conflict of interest statement

Disclosures:

C.C.R. has received research support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, has served on the medical advisory boards of Talecris Corporation and Baxter Therapeutics, and has received a research grant from Baxter Therapeutics.

S.T. is a founder and on the Board of Directors of Prometheus RxDx, Inc.

J.E.Y., S.S.R., G.U., C.L., H.L.M., S.M.H., W.Q., N.H., and L.M. have declared that they have no conflict of interest.

Figures

Figure 1
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
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
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
See this image and copyright information in PMC

References

    1. Holland SM. Chronic Granulomatous Disease. Clin Rev Allergy Immunol. 2009 - PubMed
    1. Malech HL, Hickstein DD. Genetics, biology and clinical management of myeloid cell primary immune deficiencies: chronic granulomatous disease and leukocyte adhesion deficiency. Curr Opin Hematol. 2007;14:29–36. - PubMed
    1. Yu G, Hong DK, Dionis KY, Rae J, Heyworth PG, Curnutte JT, Lewis DB. Focus on FOCIS: the continuing diagnostic challenge of autosomal recessive chronic granulomatous disease. Clin Immunol. 2008;128:117–126. - PubMed
    1. Jones LB, McGrogan P, Flood TJ, Gennery AR, Morton L, Thrasher A, Goldblatt D, Parker L, Cant AJ. Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol. 2008;152:211–218. - PMC - PubMed
    1. Matute JD, Arias AA, Wright NA, Wrobel I, Waterhouse CC, Li XJ, Marchal CC, Stull ND, Lewis DB, Steele M, Kellner JD, Yu W, Meroueh SO, Nauseef WM, Dinauer MC. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood. 2009;114:3309–3315. - PMC - PubMed

Publication types

MeSH terms