calprotectin in health &disease.

1. Kurdistan Board GEH/GIT Surgery J Club 2021
Supervised by Professor Dr. Mohamed Alshekhani.

2. Introduction:
 IBD emerged with Westernisation of dietary habits worldwide.
 CD/UC are chronic debilitating conditions that afflict individuals with
substantial morbidity& challenge healthcare systems across the globe.
 CP identified&characterized in the 1980s& emerged as significantly
validated, non-invasive biomarker of gut inflammation, discriminates
between inflammatory&non-inflammatory diseases of the gut& portraits
the disease course of human IBD.
 There are biological functions of the subunits S100A8& S100A9 during
orchestration of an inflammatory response at mucosal surfaces across
organ systems.

3. Introduction:
 Both subunits, S100A8 / S100A9, harbour a broad spectrum of
intracellular & extracellular immunomodulatory properties
 It is still debated whether the biological function of the S100A8 subunit
may be opposed to that of S100A9 in tissue inflammation& tumorigenesis.
 Considering the transcriptional regulation & biological functions of CP
during inflammation, clinicians should be aware that other conditions,
most commonly GI (bacterial or viral) infections, malignancies, drugs &
GVHD, are paralleled by increased faecal CP concentrations.
 Faecal CP represents an extensively validated biomarker for the diagnosis
&longitudinal evaluation of IBD reflecting endoscopic dis activity well.
 Intermediate faecal CP concens of 150–250 μg/g frequently challenging to
interpret in IBD(grey zone), while<40 μg/g rules out IBD& >250 μg/g
should prompt evaluation for IBD or raise suspicion for an IBD flare.
 A better understanding of the biological functions of CP particularly the
S100A8/ S100A9 subunitswill lead to novel diagnostic therapeutic advance.

8. CP&gut inflammation:
 (1) IBD arise from disrupted host-microbe interplay.
 (2) Tissue inflammation is driven by cytokines (yellow) activating innate
&adaptive immunity.
 (3) Acute inflammation leads to the mucosal recruitment of neutrophil
granulocytes (violet) which partly migrate into gut lumen& constitutively
express& release calprotectin (blue) which may fuel mucosal inflammation,
as itdrives neutrophil chemotaxis, expression of endothelial adhesion
molecules&pattern recognition receps (e.g. Toll-like receptor 4 or receptor
for AGEPs) on innate&adaptive immune cells.
 CP in neutrophils modulates tissue adherence by microtubule rearrange
(green)& cytotoxicity by generation of reactive O2 specs via NADPH Oase.
 (4) CP being antimicrobial chelates essential divalent metal ions
(e.g.calcium,Fe or Z) limiting growth of invasive&commensal gut bacteria.
 (5) CP; non-invasive (systemic/faecal) inflammatory biomarker in IBD due
to its stability at room temp, assay reproducibility& low costs,but raised in
infs, other GI diseases& in drug-induced enteropathy.