Biomarker discovery for Crohn disease and ulcerative colitis diagnosis using SELDI-TOF-MS

Crohn Disease ( CD) and Ulcerative Colitis (UC) both generally known as Inflammatory Bowel Disease (IBD) are chronic autoimmune inflammatory pathologies affecting the gastro intestinal tract. Their ethiopathogenesis has not been fully elucidated and involve a complex interplay among genetic, environmental, pathogenic and immune factors. The still growing knowledge in the ethiology of these disorders gave rise to new promising treatments. Nevertheless, the success of those drugs are cases dependent: CD or UC. Therefore, accurate and early diagnosis is a real important step in circumventing these pathologies.

Today, clinical diagnosis are made on many biological data such as CRP, ASCA, ANCA determinations, according to severity of symptoms ( recorded in Harvey-Bradshow test) or with invasive techniques as gastro-endoscopies. No simple, rapid, unique and efficient technique is able to discriminate IBD from other inflammatory diseases (as infectious colitis) or among IBD itself: CD versus UC. Here, we present a strategy of sera protein profiling on SELDI-TOF ( Surface Enhanced Laser Desorption-Ionization, Time of Flight Mass Spectrometry ) and the downstream statistical analysis.

We analyzed protein profiles obtained from four categories of patients: CD, UC, NI ( healthy controls) and I (other inflammatory diseases).We analyzed results by means of two different statistical approaches : p Value determination on integrated peaks and calculation of multiple decision trees, named "Extra-Trees" and "boosting" (Geurts et al , 2004) built on total data set or on integrated peaks. We obtained a predictive model of classification which is up to more than 85% specific and sensitive. This algorithm has also been able to show the importance of each data (or peaks) in answering the addressed question. This could lead, after cross validation, blind tests on new samples batches, to a very robust and easy-to-use diagnosis tool and than offers a powerful solution to this current need. Moreover, the purification and identification of the protein associated to the peak could help us to better understand such diseases and to highlight new therapeutic targets.