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Spatial and Temporal Stability of Paneth Cell Phenotypes in Crohn's Disease: Implications for Prognostic Cellular Biomarker Development

Liu, Ta-Chiang MD, PhD*; Gao, Feng MD, PhD; McGovern, Dermot P. B. MD, PhD‡,§; Stappenbeck, Thaddeus S. MD, PhD*

Inflammatory Bowel Diseases:
doi: 10.1097/01.MIB.0000442838.21040.d7
Original Clinical Articles
Abstract

Background: We previously demonstrated that morphologic defects of ileal Paneth cells correlate with multiple susceptible genetic variants, the presence of granuloma, and clinical outcome in Crohn's disease. These studies were performed using uninvolved areas of resection specimens. To develop Paneth cell phenotype as a prognostic biomarker in Crohn's disease, further characterization is necessary. Specifically, effects of disease activity, phenotype duration, and the minimal crypt number that would allow for accurate Paneth cell phenotyping are unknown.

Methods: We compared Paneth cell phenotypes in (1) 46 cases with paired involved and uninvolved sections; (2) 36 cases with multiple ileal resections over time; (3) “virtual biopsies” by randomly selecting 10 to 60 crypts from 85 surgical cases where 250 crypts had been analyzed; and (4) 26 cases with resection and biopsy performed within 1 year.

Results: In paired resection specimens, the Paneth cell phenotypes in the uninvolved areas correlated with those seen in involved areas (P < 0.0001) and also predicted the presence of granuloma (P = 0.042). Importantly, the Paneth cell phenotype remained stable over time (P < 0.0001). By mathematical analyses, a minimum of 40 crypts was required to generate results equivalent to those using resection specimens. Finally, there was good correlation in Paneth cell phenotypes in biopsy specimens and resection specimens obtained within 1 year (P = 0.0004).

Conclusions: Accurate Paneth cell phenotypes can be assessed using biopsy materials with the caveat that sufficient well-oriented crypts exist in the specimen. This advance will extend the potential clinical application of this novel stratification platform.

In Brief

Article first published online 18 February 2014

Author Information

*Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri;

Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri;

The F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and

§Medical Genetics Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

Reprints: Thaddeus S. Stappenbeck, MD, PhD, Department of Pathology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8118, St. Louis, MO 63110 (e-mail: stappenb@pathology.wustl.edu).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).

The research was funded by The Helmsley Charitable Trust, a Washington University Institute of Clinical and Translational Sciences Pilot Award (CTSA308) and the CCFA Genetics Initiative. Research at Cedars-Sinai is supported by USPHS grant PO1DK046763 and the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute Research Funds. D. P. B. McGovern is supported by the European Union, the CCFA, the Joshua L. and Lisa Z. Greer Chair in IBD Genetics, and grants DK062413, DK046763-19, AI067068, AI084887, and HS021747.

The authors have no conflicts of interest to disclose.

Received December 19, 2013

Accepted December 28, 2013

© Crohn's & Colitis Foundation of America, Inc.

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