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

J Pediatr Gastroenterol Nutr. 2018 May;66(5):767-772. doi: 10.1097/MPG.0000000000001851.

Abstract

Objectives: Elevated granulocyte-macrophage colony-stimulating factor auto-antibodies (GM-CSF Ab) are associated with increased intestinal permeability and stricturing behavior in Crohn 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 with 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] μg/mL vs 0.7 [0.3, 1.6] μg/mL, P = 0.0002). The frequency of elevated serum GM-CSF Ab concentration ≥1.6 μg/mL was increased in unaffected siblings of CD probands with elevated GM-CSF Ab, compared with unaffected siblings of CD probands without elevated GM-CSF Ab (33% vs 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, whereas 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / blood*
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Inflammatory Bowel Diseases / blood*
  • Inflammatory Bowel Diseases / immunology
  • Male
  • Phenotype
  • Young Adult

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Granulocyte-Macrophage Colony-Stimulating Factor