Serum levels of sCD14 and LBP as marker of non celiac gluten sensitivity

by luciano

Non-celiac gluten sensitivity is difficult to identify due to the lack – until now – of markers that can identify it. To date, in fact, the only way to diagnose it is diet by exclusion; not an easy method also because the symptoms of non-celiac gluten sensitivity overlap with those of other gastrointestinal disorders. The study presented below has highlighted a strong correlation between non-celiac gluten sensitivity and the presence of two specific markers: new perspectives are therefore opening up for a better and more accurate diagnosi

“A new study may explain why people who do not have celiac disease or wheat allergy nevertheless experience a variety of gastrointestinal and extra-intestinal symptoms after ingesting wheat and related cereals. The findings suggest that these individuals have a weakened intestinal barrier (leaky gut), which leads to a body-wide inflammatory immune response.
The study, which was led by researchers from Columbia University Medical Center were reported in the journal Gut. In the study, the researchers examined 80 individuals – 40 individuals with celiac disease, and 40 with gluten-sensitivity. Despite the extensive intestinal damage associated with celiac disease, blood markers of innate systemic immune activation were not elevated in the celiac disease group. This suggests that the intestinal immune response in celiac patients is able to neutralize microbes or microbial components that may pass through the damaged intestinal barrier, thereby preventing a systemic inflammatory response against highly immunostimulatory molecules.
The gluten-sensitivity group was markedly different. They did not have the intestinal cytotoxic T cells seen in celiac patients, but they did have a marker of intestinal cellular damage that correlated with serologic markers of acute systemic immune activation. The results suggest that the identified systemic immune activation in NCWS is linked to increased translocation of microbial and dietary components from the gut into circulation, in part due to intestinal cell damage and weakening of the intestinal barrier.
Importantly, the researchers found that the gluten sensitive subjects who followed a diet that excluded wheat and related cereals for six months were able to normalize their levels of immune activation and intestinal cell damage markers. This suggests that by testing for leaky gut syndrome it may be possible to identify individuals who would benefit from the dietary changes.

What are the new findings?
▸ Reported sensitivity to wheat in the absence of coeliac disease is associated with significantly increased levels of soluble CD14 and lipopolysaccharide-binding protein, as well as antibody reactivity to microbial antigens, indicating systemic immune activation.
▸ Affected individuals have significantly elevated levels of fatty acid-binding protein 2 that correlates with the markers of systemic immune activation, suggesting compromised intestinal epithelial barrier integrity.
How might it impact on clinical practice in the foreseeable future?
▸ The results demonstrate the presence of objective markers of systemic immune activation and gut epithelial cell damage in individuals who report sensitivity to wheat in the absence of coeliac disease.
▸ The data offer a platform for additional research
directed at assessing the use of the examined markers for identifying affected individuals and/or monitoring the response to treatment, investigating the underlying mechanism and molecular triggers responsible for the breach of the epithelial barrier,
and evaluating novel treatment strategies in affected individuals.

In summary, the results of this study on individuals with sensitivity to wheat in the absence of coeliac disease demonstrate (1) significantly increased serum levels of sCD14 and LBP, as well as antibody reactivity to microbial antigens, indicating systemic immune activation; (2) an elevated expression of FABP2 that correlates with the systemic immune responses to bacterial products, suggesting compromised intestinal epithelial barrier integrity and increased microbial translocation; and (3) a significant change towards normalisation in the levels of the immune activation markers, as well as FABP2 expression, in response to the restrictive diet, which is associated with improvement in symptoms. Our data establish the presence of objective markers of systemic immune activation and epithelial cell damage in the affected individuals. The results of the multivariate data analysis suggest that a selected panel of these may have use for identifying patients with NCWS or patient subsets in the future. It is important to emphasise that this study does not address the potential mechanism or molecular trigger(s) responsible for driving the presumed loss of epithelial barrier integrity and microbial translocation. Further research is needed to investigate the mechanism responsible for the intestinal damage and breach of the epithelial barrier, assess the potential use of the identified immune markers for the diagnosis of affected individuals and/or monitoring the response to specific treatment strategies, and examine potential therapies to counter epithelial cell damage and systemic immune activation in affected individuals”.

(1) – LBP is a 65-kDa soluble acute-phase protein mainly produced by hepatocytes5, intestinal epithelial cells6, and visceral adipocytes7. Recent studies demonstrated that serum LBP level correlates positively with obesity8, metabolic syndrome9, type 2 diabetes10,11, and atherosclerosis12,13

(2) – Soluble CD14 subtype (sCD14-ST) is is a glycoprotein expressed on the surface of monocytes and macrophages.

More…..This prospective observational study evaluated soluble CD14 subtype (sCD14-ST) as an early diagnosis and monitoring biomarker for neonatal sepsis in controls, patients with sepsis, or systemic inflammatory response syndrome (SIRS)