Development of the GlycoFibrotyper for detection of liver fibrosis

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Increasingly, alterations in N-linked glycans have been reported for serum or plasma, or for the most abundant serum glycoprotein, immunoglobulin G, from large cohorts of samples representing rheumatoid arthritis, digestive diseases, cancer and liver fibrosis. In the case of fibrosis, two tests have identified alterations in N- linked glycosylation on both total IgG populations and on specific IgG molecules. Both of these tests can detect significant fibrosis with a high degree of accuracy and are also able to detect intermediate levels of fibrosis. However, both tests have drawbacks in that they require specialized sample handling resources, extensive processing and purification prior to analysis, and are expensive in regards to reagents and processing. Our group has recently developed a streamlined antibody capture slide array approach to directly profile N-glycans of captured serum glycoproteins like IgG, a method requiring a few microliters of sample and simplified processing workflows that require no purification or sugar modifications prior to analysis. This parent method is referred to as the GlycoTyper. In this method, N-linked glycans are released from antibody captured glycoproteins and are directly analyzed by MALDI-TOF mass spectrometry, such as the Bruker Tissuetyper MALDI-TOF, which is already available in clinical laboratories. We hypothesize that this method can be used to identify glycan biomarkers reflective of the changes that occur during the development of many diseases, including liver fibrosis/cirrhosis as performed here.