Gastroenterology

Gastroenterology

Volume 149, Issue 5, October 2015, Pages 1275-1285.e2
Gastroenterology

Review
Biomarkers From Blood and Stool
Biomarkers of Inflammation in Inflammatory Bowel Disease

https://doi.org/10.1053/j.gastro.2015.07.003Get rights and content

Recent observations suggest that subjective measures of disease activity in inflammatory bowel disease (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 computed tomography or magnetic resonance imaging. Noninvasive, accurate, and inexpensive measures of intestinal inflammation would allow clinicians to adopt widely the paradigm of adjusting therapies with a goal of controlling inflammation. Blood, stool, and urine markers have all been explored as indicators of intestinal inflammation in IBD, and although none has been universally adopted, some have been well-characterized, and others hold great promise. Serum C-reactive protein and fecal calprotectin are among the best-studied noninvasive biomarkers of inflammation in IBD, and their test characteristics have been described in the setting of differentiating IBD from irritable bowel syndrome, for grading inflammation, to describe the response to therapy, and in demonstrating recurrent inflammation after medical or surgically induced remission. High-throughput research platforms, including gene expression arrays, metabolomics and proteomics, are also being applied to the discovery of novel biomarkers of inflammation. It is certain that biomarkers of inflammation will attain growing importance in the clinic as we strive for more effective and cost-effective strategies to treat patients with IBD.

Section snippets

Serum and Blood Markers

The intense bowel inflammation of IBD is accompanied by an acute phase response detectable in the serum and blood. The acute phase response is characterized by increased elaboration of proteins involved in coagulation and fibrinolysis, such as fibrinogen, plasminogen, Factor VIII, and prothrombin; complement system components such as C1 inhibitor, C1s, C2, C3, C4, C5 and C9; proteinase inhibitors, including α-1-antitrypsin, α1 anti-chymotrypsin; transport proteins such as haptoglobin and

Stool Markers

As compared to blood or serum biomarkers, stool markers have the advantage of increased specificity for inflammatory processes localized to the bowel. While some fecal markers, such as α-1-antitrypsin and occult blood, reflect disruption of the mucosal barrier, such markers are not as accurate as others that are associated with the pathogenic inflammatory processes underlying IBD.13 Products of leukocyte degranulation, such as lysozyme, myeloperoxidase, eosinophilic cationic protein,

Urine Markers

A small number of substances excreted in urine have been investigated as biomarkers of inflammation in IBD. These include a variety of prostaglandin and leukotriene pathway products,18, 19, 20, 21 neutrophil gelatinase-associated lipocalin,22 alpha 1-acid-glycoprotein and Zn-alpha 2-glycoprotein,23 and neopterin.24 None is extensively validated, and none is in common use in the clinic.

Clinical Utility

Inflammation biomarkers may be useful in a variety of important clinical scenarios (see Figure 1 for applications of biomarkers of inflammation in CD). In the broadest sense, inflammation biomarkers have been used in IBD for 2 main purposes: (1) identifying patients with symptoms of IBD who should be further investigated for a possible IBD diagnosis; and (2) measuring or monitoring disease activity in response to induction or maintenance therapy. The latter purpose includes diverse settings,

Future Approaches

The search continues for more specific, sensitive, and responsive markers of inflammation to assist in the management of IBD. This effort has been accelerated by the recent availability of high-throughput discovery platforms, capable of measuring thousands of analytes simultaneously. These include gene expression arrays, and metabolomic and proteomic platforms.

Conclusions

Driven by a significant need in the clinic for accurate and noninvasive means to measure intestinal inflammation objectively, biomarkers of inflammation have been the subject of intense investigation in IBD. Increasingly, blood and stool markers such as CRP and calprotectin are being used in practice as measures of intestinal inflammation, with a growing understanding of their utility and limitations. Further studies are needed to improve understanding of these markers as surrogates for the

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    Conflicts of interest The author discloses the following: received fees for consulting or speaking in CME programs received from AbbVie; Amgen; AstraZeneca; Avaxia Biologics; Bristol-Myers Squibb; Curatio CME Institute; Focus Medical Communications; Janssen Biotech; Millennium Pharmaceuticals/Takeda; Pfizer; Prometheus Laboratories; Puretech Ventures, LLC; Salix; Shire; Topivert Pharma; Luitpold Pharmaceuticals; MedImmune; Immune Pharmaceuticals; IMEDEX; Vindico Medical Education; Akros Pharma; Rockpointe; Strategic Consultants International; TiGenix; Celgene; research support from AbbVie; Amgen; AstraZeneca; Centers for Disease Control and Prevention; Crohn's & Colitis Foundation of America; Janssen Biotech; Millennium Pharmaceuticals/Takeda; Celgene; Pfizer; Prometheus Laboratories; and holds stock in Avaxia Biologics (non-publicly traded stock) and ETX Pharma (non-publicly traded stock).

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