Gut immunoglobulin alpha anti-glycan binding profiles as a research tool for local disease detection.

A promising approach capitalizing on the specific and highly sensitive characteristics of the body's own immune system is demonstrated in the context of revealing pancreatic ductal adenocarcinoma cancer (PDAC). IgA from a local biofluid called gastrointestinal lavage fluid (GLF) is used to investigate glycan reactivity to show the potential of this approach. IgA antibody responses, just as with IgG, result in amplification of a small signal which aids in detecting changes from a healthy state. IgA from GLF was screened against glycan arrays containing 609 glycan structures to investigate differential binding patterns associated with the disease. Samples included PDAC (n = 14) and non-PDAC (n = 6). Non-PDAC conditions included samples from healthy patients and the potentially confounding conditions of colon cancer and its precancerous lesion, colon adenoma. Results demonstrated characteristic reactivity in the PDAC sample group to a glycan structure. Also, IgA non-reactive motifs arose showing remarkable consistency within and between sample groups. While sample sizes are too small to identify putative biomarkers, these data show the use of IgA from GLF to be a promising avenue of research for local disease biomarker discovery.

Comparative Proteomic Analysis of Whole-Gut Lavage Fluid and Pancreatic Juice Reveals a Less Invasive Method of Sampling Pancreatic Secretions.

OBJECTIVES: There are currently no reliable, non-invasive screening tests for pancreatic ductal adenocarcinoma. The fluid secreted from the pancreatic ductal system ("pancreatic juice") has been well-studied as a potential source of cancer biomarkers. However, it is invasive to collect. We recently observed that the proteomic profile of intestinal effluent from the bowel in response to administration of an oral bowel preparation solution (also known as whole-gut lavage fluid, WGLF) contains large amounts of pancreas-derived proteins. We therefore hypothesized that the proteomic profile is similar to that of pancreatic juice. In this study, we compared the proteomic profiles of 77 patients undergoing routine colonoscopy with the profiles of 19 samples of pure pancreatic juice collected during surgery. METHODS: WGLF was collected from patients undergoing routine colonoscopy, and pancreatic juice was collected from patients undergoing pancreatic surgery. Protein was isolated from both samples using an optimized method and analyzed by LC-MS/MS. Identified proteins were compared between samples and groups to determine similarity of the two fluids. We then compared our results with literature reports of pancreatic juice-based studies to determine similarity. RESULTS: We found 104 proteins in our pancreatic juice samples, of which 90% were also found in our WGLF samples. The majority (67%) of the total proteins found in the WGLF were common to pancreatic juice, with intestine-specific proteins making up a smaller proportion. CONCLUSIONS: WGLF and pancreatic juice appear to have similar proteomic profiles. This supports the notion that WGLF is a non-invasive, surrogate bio-fluid for pancreatic juice. Further studies are required to further elucidate its role in the diagnosis of pancreatic cancer.

Rectal effluent as a research tool.

Studies of localized secretions are generally superior to those of blood because they contain higher concentrations of molecules specific to the organ of interest. A common method used to analyze localized secretions is lavage. The flow of fluid over the lining of a cavity picks up both cells and soluble factors, and the effluent can be collected for study. Gastrointestinal (GI) lavage is easily and noninvasively performed by the administration of gut lavage solutions such as those routinely given to patients prior to colonoscopy, with GI lavage fluid being the copious, watery rectal effluent subsequently induced. Residual effluent is currently suctioned from the colon and discarded during colonoscopy. With millions of routine colonoscopies performed per year, GI lavage fluid is a rich and largely untapped resource for basic and clinical research. Rectal effluent can also be easily collected in a toilet receptacle without need for a colonoscopy. Rectal effluent generated in this manner has been used to study diarrheal disease, mucosal immunology, inflammatory bowel disease, celiac disease, and cancer. It is often referred to as gut lavage, colon lavage, GI lavage, or whole gut lavage fluid, which makes it challenging to locate previous studies in the literature and there are currently no comprehensive reviews of its use as a research tool. This review attempts to fill this void by discussing previous applications of rectal effluent in research and the methods that have been developed for its collection, stabilization, and analysis.