Familial Association of Granulocyte-Macrophage Colony Stimulating Factor Autoantibodies in Inflammatory Bowel Disease

ABSTRACT Objectives: Elevated Granulocyte-Macrophage Colony Stimulating Factor auto-antibodies (GM-CSF Ab) are associated with increased intestinal permeability and stricturing behavior in Crohn's Disease (CD). We tested for familial association of serum GM-CSF Ab level in CD and Ulcerative Colitis (UC) families. Methods: Serum GM-CSF Ab concentration was determined in 230 pediatric CD probands and 404 of their unaffected parents and siblings, and 45 UC probands and 71 of their unaffected parents and siblings. A linear mixed effects model was used to test for familial association. The Intra-class correlation coefficient (ICC) was used to determine the degree of association of the serum GM-CSF Ab level within families in comparison to the degree of association among families. Results: The median (IQR) serum GM-CSF Ab concentration was higher in CD probands than in UC probands (1.5(0.5,5.4) mcg/mL versus 0.7(0.3,1.6) mcg/mL, p = 0.0002). The frequency of elevated serum GM-CSF Ab concentration ≥ 1.6 mcg/mL was increased in unaffected siblings of CD probands with elevated GM-CSF Ab, compared to unaffected siblings of CD probands without elevated GM-CSF Ab (33% versus 13%, respectively, p = 0.04). A similar result was observed within UC families. In families of CD patients, the mean (95th CI) ICC was equal to 0.153 (0.036,0.275), p = 0.001, while in families of UC patients, the mean (95th CI) ICC was equal to 0.27(0.24,0.31), p = 0.047. Conclusions: These data confirmed familial association of serum GM-CSF Ab levels. This could be accounted for by either genetic or environmental factors shared within the family. Address correspondence and reprint requests to Lee A. Denson, MD, MLC 2010, 3333 Burnet Avenue, Cincinnati, OH 45229-3026 (E-mail: lee.denson@cchmc.org). Received 7 October, 2016 Accepted 10 August, 2017 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). Conflicts of Interest and Source of Funding. Dr. Denson has received research support from Janssen to study GM-CSF Ab. This work was supported by NIH/NIDDK via R01DK078683 (LAD), R01DK098231 (LAD & SK), and T32 DK007727 (SSW and AT). Word count: 3226; two tables and two figures Author Contributions: Sandra S. Wright, MD: study design, data acquisition, drafting of the work, and final approval. Anna Trauernicht, MD: study design, data acquisition, revising of the work, and final approval. Erin Bonkowski, BA: data acquisition, revising of the work, and final approval. Courtney A. McCall, BS: data acquisition, revising of the work, and final approval. Elizabeth A. Maier, BS: data acquisition, revising of the work, and final approval. Ramona Bezold, BSN: data acquisition, revising of the work, and final approval. Kathleen Lake, MSW: data acquisition, revising of the work, and final approval. Claudia Chalk, BS: data acquisition, revising of the work, and final approval. Bruce C. Trapnell, MD: study design, data interpretation, revising of the work, and final approval. Mi-Ok Kim, PhD: study design, data analysis & interpretation, revising of the work, and final approval. Subra Kugathasan, MD: study design, data interpretation, revising of the work, and final approval. Lee A. Denson, MD: study design, data interpretation, revising of the work, and final approval. © 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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