1000-plex antibody array proteomic screen uncovers PGRPS, Haptoglobin, Serpin A4 and Fibrinogen as potential stool biomarkers of pediatric inflammatory bowel disease

• Published in: Clinical immunology (Orlando, Fla.) Vol. 276; p. 110495
• Main Authors: Pereira, Ryan, Soomro, Sanam, Vanarsa, Kamala, Castillo, Jessica, Maruvada, Vinaika, Kugathasan, Subra, Mohan, Chandra
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2025
• Subjects: Adolescent; Biomarkers; Biomarkers - analysis; Biomarkers - metabolism; Child; Colitis, Ulcerative - diagnosis; Colitis, Ulcerative - metabolism; Crohn Disease - diagnosis; Crohn Disease - metabolism; Crohn's disease; Cross-Sectional Studies; Fecal proteomics; Feces - chemistry; Female; Fibrinogen - analysis; Fibrinogen - metabolism; Haptoglobins - analysis; Haptoglobins - metabolism; Humans; Inflammatory bowel disease; Inflammatory Bowel Diseases - diagnosis; Inflammatory Bowel Diseases - metabolism; Male; Proteomics - methods; Serpins - metabolism; Ulcerative colitis; Inflammatory bowel disease; Biomarkers; Fecal proteomics; Crohn's disease; Ulcerative colitis
• DOI: 10.1016/j.clim.2025.110495
• ISSN: 1521-6616; 1521-7035

Easy to obtain and in close proximity to the affected areas, fecal samples offer significant potential for the advancement of non-invasive diagnostic methods for inflammatory bowel disease (IBD). A cross-sectional antibody array-based proteomic screen of 1000 fecal protein biomarkers was conducted using stool from treatment naïve control, Crohn's disease (CD), and ulcerative colitis (UC) subjects (control = 24, CD = 39, UC = 10). 71 proteins were significantly elevated in IBD stool (p < 0.05; FC > 2), pointing to cytokine signaling, inflammatory response and extra-cellular matrix functional pathways. Several proteins outperformed fecal calprotectin in distinguishing IBD from control stool, including Haptoglobin, IL-1 R9, GDF-15, PGRPS, Serpin A4, INSRR, SSEA-1, Fibrinogen, IGFBP-1, and TGF-β RI/ALK-5. Upon ELISA validation, PGRPS (AUC = 0.96), Haptoglobin (AUC = 0.91), Serpin A4 (AUC = 0.73), emerged as the most discriminatory biomarkers. Taken together with previous cross-sectional and longitudinal studies, the present findings authenticate stool PGRPS, Haptoglobin, Serpin A4 and fibrinogen as potential stool biomarkers of UC and CD, worthy of further prospective studies to identify more reliable and accurate non-invasive biomarkers for IBD. •Currently, there is no definitive non-invasive diagnostic for pediatric IBD.•Novel fecal biomarkers may be diagnostic of pediatric inflammatory bowel disease.•Fecal Calprotectin is the current clinical gold standard.•Stool PGRPS, Haptoglobin, Serpin A4, and fibrinogen outperform Calprotectin.