Inflammatory Bowel Disease from the Perspective of Newer Innate Immune System Biomarkers

Abstract

Background: The perspective of inflammatory bowel disease (IBD) has changed radically since the first decade of the 21st century, and the formerly monolithic components of IBD, ulcerative colitis (UC), and Crohn's disease (CD) have undergone a fundamental convergence, with realization that there is likely an element of shared pathogenesis. The ground shift began with genomic revelation but with the current emergence of the innate immune system (InImS) as a key player, allowing for improved understanding of the associations between the immune underpinnings of IBD.

Methods: Using unique ferritin/fecal p87 (FERAD) or using colonoscopic effluent as denominator (FEREFF) and other ratios to test this hypothesis, we prospectively enrolled 2185 patients with increased risk of colorectal cancer, of whom 31 had UC and 18 CD, with 2136 controls and brought to bear in a convenient measure for the InImS, the FERAD ratio. The FERAD, FEREFF, and NLR ratios have been shown to be effective measures of the InImS in COVID-19 and various cancers. p87 is expressed in gut Paneth cells known to modulate the microbiome by secretion of alpha-defensins, a natural antibiotic. Other related parameters were also evaluated.

Results: There was no significant difference between the FERAD ratio in UC and CD. However, differences between IBD entities and controls were substantial.

Conclusions: InImS settings in IBD are similar between CD and UC. p87 tissue immunohistochemistry (IHC) is also shared. Other InImS markers, such as the absolute neutrophil/lymphocyte ratio, are also confluent between the two IBD forms.

Keywords: Adnab-9 antibody; Crohn’s disease; FERAD ratio; Paneth cells; immunohistochemistry (IHC); inflammatory bowel diseases; innate immune system; p87.

Figure 1.

A flow diagram showing the total number and those of the IBD patients and controls.

Figure 2.

Bar diagram depicting the comparison of FERAD levels in IBD and controls.

Figure 3.

Bar diagram showing mean levels of colonic p87 expression in disease versus controls.

Figure 4.

The crypts are well-oriented and likely represent inactive UC. The Adnab-9 antibody was used in a concentration of 1:50 dilution and developed using the ABC kit (see Section 3 below). The magnification in Figure 4 is 20×.

Figure 5.

A direct correlation exists in IBD patients between initial and final ferritin determinations.