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 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.