ANTI-GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR AUTOANTIBODIES ARE ASSOCIATED WITH DEVELOPMENT OF COMPLICATIONS IN RECENTLY DIAGNOSED CROHN’S DISEASE PATIENTS

Background: Anti-granulocyte macrophage-colony stimulating factor autoantibodies (anti-GM-CSF) have been associated with development of Crohn’s disease (CD) and complications at time of diagnosis. There are limited data on anti-GM-CSF as a prognostic biomarker in CD. We evaluated the association of anti-GM-CSF in recently diagnosed patients with clinical outcomes.

Methods: We analyzed anti-GM-CSF titers in serum samples in CD patients from the Ocean State Crohn’s and Colitis Area Registry (OSCCAR). OSCCAR is a prospective, biosample-linked, community-based inception cohort capturing new pediatric and adult CD diagnoses in Rhode Island. OSCCAR patients had longitudinal clinical data collected through structured interviews and standardized central medical record data abstraction with a median follow up of 7 years. The primary outcome was development of disease complications defined as any new stricturing (B2) / penetrating (B3) complication, perianal disease, CD-related surgery, and/or CD-related hospitalization. Anti-GM-CSF IgA and IgG to sargramostim were assayed by ELISA at all timepoints available using serial dilutions. An anti-GM-CSF reciprocal titer >100 was considering positive for the antibodies. Time to event analyses were performed. Spearman’s correlation assessed the association between anti-GM-CSF and anti-microbial antibodies at baseline. Cox regression assessed the association between the primary outcome and baseline log anti-GM-CSF IgA and IgG.

Results: 229 CD patients from OSCCAR had baseline serum assayed for anti-GM-CSF. Mean age (SD) was 29 (17.7) years, 41% were men, disease location was ileal in 22.7% and ileocolic in 31.3%, 79% had inflammatory disease behavior at baseline, and 7% had perianal disease. 11.6% of patients were positive for anti-GM-CSF IgA and 21.2% were positive for IgG. The majority of patients had stable titers over 5 years (Figure 1A). Baseline anti-GM-CSF IgA and IgG titers were associated with younger age, B2/B3 behavior, and perianal disease but not disease location (Figure 1B). Anti-GM-CSF IgA was significantly (p<0.05) correlated with Cbir (r=0.21), ASCA IgG (r=0.51), and ASCA IgA (r=0.59) and anti-GM-CSF IgG was also significantly (p<0.05) correlated with Cbir (r=0.25), ASCA IgG (r=0.61), and ASCA IgA (r=0.54). Anti-GM-CSF IgA and IgG positive patients were significantly more likely to have disease complications over time (IgA HR 1.70 [95%CI 1.01-2.72]; IgG HR 1.73 [95%CI 1.15-2.60]) (Figure 2). In multivariable models controlling for baseline ulcers, upper tract disease, history of bowel resection, and ANCA, both log anti-GM-CSF IgA and IgG were associated with the development of disease complications (IgA aHR 1.21 [95%CI 1.02-1.43]; IgG aHR 1.66 [95%CI 1.0-2.77]).

Conclusion: Anti-GM-CSF IgG and IgA are biomarkers associated with risk of developing disease complications in recently diagnosed CD patients.