Associations between Cellular Energy and Pediatric Inflammatory Bowel Disease Patient Response to Treatment

Inflammatory
bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis,
are chronic diseases of the gastrointestinal tract, with an unknown
etiology, that affect over 6.8 million people worldwide. To characterize
disease pathogenesis, proteomic and bioinformatic analyses were performed
on colon biopsies collected during diagnostic endoscopy from 119 treatment-naïve
pediatric patients, including from 78 IBD patients and 41 non-IBD
patients who served as controls. Due to the presence of noninflamed
and/or inflamed regions in IBD patients, up to two biopsies were obtained
from IBD patients as compared to a single noninflamed biopsy from
non-IBD pediatric control patients. Additional biopsies were obtained
and analyzed from 33 of the IBD patients after IBD-directed therapeutic
intervention for comparison of pre- and post-treatment proteomes.
SuperSILAC was utilized to perform quantitative analysis of homogenized
tissues, which were processed by filter-aided sample preparation.
Hierarchical clustering and principal component analyses revealed
proteomic patterns that distinguished inflamed from noninflamed tissues
independent of therapy. Gene ontology revealed that proteins downregulated
in inflammation are associated with metabolism, whereas upregulated
proteins contribute to protein processing. A comparison of pre- and
post-treatment proteomes from CD patients identified over 100 proteins
that are significantly different between patients who responded and
those who did not respond to therapy, including creatine kinase B
and basigin.