Git j club IBD biomarkers.

1. Kurdistan Board GEH J Club 2016
Dr.Mohamed Al-Shekhani
MBChB-CABM-FRCP,EBGH

2. Introduction:
• Subjective measures of disease activity in IBD are often
misleading.
• Objective measures of inflammation are more closely
associated with important long-term outcomes,but often
depend upon invasive and costly procedures such as
ileocolonoscopy and cross-sectional imaging by CT or MRI.
• Noninvasive, accurate& inexpensive measures of intestinal
inflammation would allow clinicians to adopt widely the
paradigm of adjusting therapies with a goal of controlling
inflammation.
• Blood, stool&urine markers have all been explored as
indicators of intestinal inflammation in IBD.
• Although none has been universally adopted, some have
been well-characterized&others hold great promise.

3. Introduction:
• Serum C-reactive protein & fecal calprotectin are among the
best-studied noninvasive biomarkers of inflammation in
IBD.
• Their test characteristics have been described in:
• Differentiating IBD from IBS
• For grading inflammation
• To describe the response to therapy
• In demonstrating recurrent inflammation after medical or
surgically induced remission.
• Gene expression arrays, metabolomics, proteomics, are
also being applied to the discovery of novel biomarkers of
inflammation.

4. Introduction:
• IBD: mucosal inflammation flaring remit over time.
• The outcomes may be improved by directing treatment to
the state of mucosal inflammation rather than to symptoms.
as symptoms do not consistently reflect the presence or
severity of mucosal inflammation&relying on symptoms to
guide therapy will lead to 2 important management errors:
• 1. Symptoms may be present when mucosal inflammation
is not substantially active, occur in 20% of patients with CD1
or UC2 who have no significant mucosal inflammation,
potentially leading to abandonment of effective therapy or
unnecessary escalation.
• 2. Patients with active inflammation may fail to report
symptoms, leading to under-treatment of the disease,with
progression to complications in CD, and higher likelihood of
symptomatic recurrence in both CD & UC.

5. Introduction:
• Endoscopy &imaging have notable limitations of cost,
inconvenience& invasiveness, unsuitable for frequent
monitoring.
• Lab biomarkers that is rapid, convenient, noninvasive,
inexpensive, standardized, reproducible& accurate in
reflecting the state of bowel inflammation in IBD may fill this
gap.
• Till now there is no ideal IBD biomarkers.

6. Bllod biomarkers:
• Few extensively validated in IBD& fewer in routine use.
• CRP/ESR are the most widely available/used.
• CRP has a relatively short half-life of 19 hours, making it a
more responsive indicator of acute inflammation than most
other acute phase reactants.
• Assays vary in their sensitivity & definitions of normal 0.8
mg/L for highly sensitive assays to 5 mg/L for standard
sensitivity assays.
• CRP is also expressed in mesenteric adipocytes in CD,
accounting for higher CRP in CD than in UC.
• 25% with demonstrable activity of CD on endoscopy do not
have normal CRP.
• In severe UC, elevated CRP is associated with higher
likelihood of colectomy.

9. Stool biomarkers:
• Many found to increase in relation to disease activity in IBD.
• Some limitations:
• Patients’ disinclination to collect stool.
• Lack of specificity of fecal biomarkers for IBD, as opposed
to other infectious or inflammatory processes.
• Intraindividual variability of some fecal markers, including
calprotectin, may be large
• Calprotectin/ lactoferrin have been studied more extensively
than other &readily available in clinical laboratories.

10. Urine biomarkers:
• A small number but none is extensively validated& none is
in common use in the clinic.

12. Clinical uses:1.differtiating IBD from IBS
• Patients with CRP 0.5 mg/dL or FC 40 mg/g were found to
have a 1% probability of having IBD.
• ESR / fecal lactoferrin, in isolation, did not have adequate
clinical utility in excluding IBD.
• Sensitivity of 93% &specificity of 96% for FC to diagnose
IBD (less in children), With cutoffs 24-150 mg/g of stool.

13. Clinical uses: 2. Measuring/ Monitoring Disease
Activity
• A.Categorization of Disease Activity:
• In UC, FC correlate to extent &severity of inflammation.
• In CD combination of FC, serum MMP& serum IL-22,
provided the highest correlation to inflammatory activity
compared to combined ileocolonoscopy /CTE
• The Mayo endoscopic subscore was best described by a
combination of FC&MMP.

14. Clinical uses: Measuring/ Monitoring Disease
Activity
• B.Response to treatment:
• While studies show the promise of biomarkers in tracing
individual disease activity in response to therapy, no single
biomarker has gained wide acceptance.

15. Clinical uses: Measuring/ Monitoring Disease
Activity
• C.Predicting relapse:
• FC predicts clinical relapse more in UC than in CD.
• FC was significantly correlated with relapse in colonic CD.
• FC >200 mg/g had *4 higher relapse over a year, although
the accuracy less in ileal disease.
• In UC,FC >120 mg/g *6 > to have clinical relapse.
• FC >340 mg/g was associated with *18 increase in risk of
relapse, significantly > CRP.
• S. calprotectin 5675 ng/mL, FC 250 mg/g, hsCRP 5 mg/L for
independently associated with subsequent relapse.
• FC was independently associated with risk for relapse, in
contrast to lactoferrin.
• Regular monitoring of FC to identify individuals at risk for
symptomatic flare of UC is recommended.
• FC performance was similar in UC & CD.

16. Clinical uses: Measuring/ Monitoring Disease
Activity
• D.Predicting Relapse in CD After Surgery:
• The best evidence suggests that FC, rather than recurrent
symptoms or elevation of CRP, may be best utilized as part
of a strategy to monitor for postoperative recurrence, with
values 100 mg/mg strongly suggesting no recurrent
disease, and no need to evaluate for recurrence by
ileocolonoscopy.

17. Future Approaches
• Gene expression arrays.
• Metabolomic.
• Proteomics.

20. Conclusions:
• Increasingly, blood& stool markers such as CRP/
calprotectin are being used in practice as measures of
intestinal inflammation, with a growing understanding of
their utility &limitations.
• Further studies are needed to improve understanding of
these markers as surrogates for the course of disease&
identify new biomarkers with still better test characteristics,
reduced cost & improved convenience.