Neutrophil proteins as non-invasive discriminators in bowel inflammation

Inflammatory bowel disease
Inflammatory bowel disease (IBD) refers to two chronic diseases that cause inflammation of the intestines, namely Crohn's disease (CD) and ulcerative colitis (UC). According to estimates, over 1 million people in the Unites States suffer from IBD. It occurs most frequently in people ages 15 to 30, but it can also affect younger children and older people. There are significantly more reported cases in western Europe and North America than in other parts of the world. The assessment of intestinal inflammation in patients with IBD remains a difficult challenge.

Differences between CD and UC
CD and UC have some features in common, but there are some important differences. UC is limited to the large intestine, which is infected continually, starting from the rectum. In CD, healthy and inflamed intestinal segments alternate. However, the entire digestive tract from the esophagus to the bowel end can be affected. Most frequently, the passage area between the small and the large intestine is inflamed. While only the mucous membrane is inflamed in UC, in CD deeper regions can be affected as well. Frequently, constrictions and excrescences can develop which can lead to intestinal obstruction. This can only be corrected by surgically removing parts of the intestine.
The inflammation spreads to all layers of the intestinal wall, resulting in scarring, thickening, and narrowing of the rectal tube. Often malignant growths occur that have to be surgically removed. In addition, CD can spread to surrounding tissue, such as the bladder, the vagina or the skin.

Neutrophil proteins and IBD
The presence of active gut inflammation in patients with IBD is associated with an acute phase reaction and the migration of leukocytes to the gut. Activated leucocytes infiltrate the mucosa and can be detected in feces due to shedding in the intestinal lumen. The most important leukocyte population in the intestinal wall in IBD are the polymorphonuclear cells (PMNs). These PMNs, also called neutrophils, accumulate within epithelial crypts and in the intestinal mucosa directly correlating with clinical disease activity and epithelial injury in IBD. Therefore, neutrophil proteins are perfect targets for noninvasive screening of IBD patients. Neutrophils generate an arsenal of proteins with antimicrobial activities among which alpha-defensin 1-3, lactoferrin, calprotectin (S100A8/S100A9), PMN-elastase, lysozyme and myeloperoxidase (MPO). All of these proteins are produced in significant amounts by inflammatory cells and can be detected not only in plasma, but also in feces. In fact, high fecal neutrophil proteins levels have been detected in IBD patients and may be used as surrogate markers of active disease. Particularly lactoferrin and calprotectin, have been demonstrated to be useful in detecting active inflammatory bowel disease, in predicting recurrence of disease after surgery or monitoring the effects of medical therapy. Calprotectin and lactoferrin are remarkably stable and easily detectable in stool using ELISA. They appear to be equally recommendable as inflammation markers in the lower gastrointestinal tract especially in IBD patients.

Progress in IBD research
The assessment of intestinal inflammation in patients with IBD remains a difficult challenge. For accurate monitoring intestinal inflammation, symptoms and clinical examinations are combined with endoscopy with histology, additional radiological, or cross-sectional imaging techniques. Novel accurate non-invasive markers are warranted, since available laboratory markers as ESR and CRP are non-specific and thus elevated upon inflammation independent of the location. During the last decade, IBD research has made major progress revealing potential non-invasive markers. Recent investigations unmask the importance of neutrophil markers like calprotectin, PMN-elastase, lactoferrin, lysozyme, alpha-defensin 1-3 (HNP1-3) and MPO in distinguishing active IBD from inactive IBD and irritable bowel syndrome (IBS).
Additional research will confirm the potent capabilities of the neutrophil proteins like lactoferrin, calprotectin and elastase as non-invasive markers for distinguishing active inflammatory bowel disease from other causes of bowel dysfunction.

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