Granulocyte Macrophage Colony-Stimulating Factor Auto-Antibodies and Disease Relapse in Inflammatory Bowel Disease

OBJECTIVES: Along with others, we have reported that neutralization of granulocyte macrophage colony-stimulating factor (GM-CSF) increases intestinal permeability and bacterial translocation, and reduces neutrophil bacterial killing and anti-microbial seroreactivity. The objective was to investigate the utility of serum GM-CSF auto-antibody (Ab) as a marker for confirmation of stable remission and prediction of relapses in patients with inflammatory bowel disease (IBD). METHODS: We consecutively included 181 adults and children with Crohn's disease (CD, n = 61) or ulcerative colitis (UC, n = 120). Over a 3-year period, we collected 861 serum samples and 610 stool samples during regular follow-up visits. GM-CSF Abs and fecal S100 proteins were measured by an enzyme-linked immunoassay. RESULTS: Serum GM-CSF Ab levels correlated with disease activity, location, and extent. Time course analysis before and after relapse showed a clear increase of GM-CSF Ab concentrations up to 6 months before clinical relapse. At 1.7 mu g/ml (CD) and 0.5 mu g/ml (UC), the sensitivity and specificity of GM-CSF Ab for predicting relapse already 2-6 months earlier were 88 % and 95 % in CD and 62 % and 68 % in UC, respectively. A baseline GM-CSF Ab level of >1.7 mu g/ml was significantly associated with relapse of CD within 18 months. CONCLUSIONS: As GM-CSF is required for myeloid cell antimicrobial functions and homeostatic responses to tissue injury, serum GM-CSF Ab levels might reflect the degree of bowel permeability and bacterial translocation. Therefore, GM-CSF Ab might identify IBD patients at risk of disease relapse at an early stage, which makes the test a potential tool for monitoring disease activity and optimizing therapy.