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

Abstract

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.

Serum antibody screening using glycan arrays

“…Beyond screening serum, the 609-component CFG glycan array has also been used to screen IgA in gastrointestinal lavage fluid samples isolated from pancreatic cancer patients ( n = 14) and controls ( n = 6). 258 The authors focus on IgA because mucosal-associated lymphoid tissue in the GI tract is hypothesized to secrete IgA against pancreatic cancer glycoproteins. Interestingly, half of the antibody signals observed to be elevated in pancreatic cancer patients targeted glycans sharing a terminal GlcNAcα1-4Galβ1-4GlcNAc motif.…”

Glycan-specific antibodies as potential cancer biomarkers: a focus on microarray applications

“…Although the sampling of patients was small and amounted to only 20 volunteers, the authors were able to identify a group of glycans, and the levels of antibodies to these glycans were increased in patients with pancreatic cancer. Most of these glycans contained the terminal motif of GlcNAcα1-4Galβ1-4GlcNAc, which is a component of the lipopolysaccharide from Proteus mirabilis, a potentially pathogenic bacterium often found in the intestine [76]. This may be due to the link among inflammation caused by this bacterium, the production of interleukin 1 β, changes in the microbiome and carcinogenesis [114].…”