Glycomics, extracellular matrix, and anti-glycan antibodies in exfoliation syndrome.

Exfoliation syndrome (XFS) is considered to be a disease of extracellular matrix. Here we review key experimental evidence of aberrations in structure, expression, and function of glycoproteins, complex carbohydrates, and glycosaminoglycans found in extracellular matrix components forming exfoliation material in patients presenting with XFS. We hypothesize that certain components of the accumulating exfoliation material can become immunogenic, and multiple natural antibodies or autoantibodies are generated. Anti-glycan antibodies (AGAs) can be captured on Printed Glycan Array. Our preliminary results show robust immunoprofiles of AGAs in sera of patients with XFS, and the significant presence of AGAs in aqueous humor of these patients. These findings offer insight into the dynamics of AGAs during the development of XFS that could lead to the identification of the AGA-based XFS immuno-signature.

Serum antiglycan antibody detection of nonmucinous ovarian cancers by using a printed glycan array.

Epithelial ovarian cancer has the highest mortality rate among gynecological cancers. Altered glycosylation is associated with oncogenic transformation producing tumor-associated carbohydrate antigens. We investigated the potential of natural occurring antiglycan antibodies in the diagnosis of ovarian cancer by using printed glycan array. Antiglycan antibodies bound to 203 chemically synthesized printed glycans were detected via biotin-streptavidin fluorescence system in serum of women with normal operative findings (healthy controls; n = 24) and nonmucinous borderline or ovarian cancer of various FIGO stages (n = 33). Data were validated measuring blood group associated di-, tri and tetrasaccharide antigens on known ABO blood groups. Antiglycan antibodies demonstrated high reproducibility (r(c) > 0.9). Cluster analysis identified repetitive patterns of specific core carbohydrate structures: 11 N-linked glycans, 3 O-linked glycans and 2 glycosphingolipids. Biomarker detection revealed 24 glycans including P(1) (Galα1-4Galß1-4GlcNAcß; p < 0.001) significantly discriminating between (low-) malignant tumors and healthy controls. Comparable sensitivity and specificity with tumor marker CA125 was achieved by a panel of multivariate selected and linear combined antiglycan antibody signals (79.2 and 84.8%, respectively). Our findings demonstrate the potential of glycan arrays in the development of a new generation of biomarkers for ovarian cancer.

Processing and analysis of serum antibody binding signals from Printed Glycan Arrays for diagnostic and prognostic applications.

Procedures for data preprocessing, quality control, data analysis, evaluation and visualization of the new high-throughput biomarker platform based on printed glycan arrays (PGA) are presented in this paper. PGAs are similar in concept to DNA arrays but contain deposits of various carbohydrate structures (glycans) instead of spotted DNAs. PGA biomarker discovery for the early detection, diagnosis and prognosis of human malignancies and viral diseases is based on the response of the immune system as measured by the level of binding of anti-glycan antibodies from human serum to the glycans on the array. Procedures related to PGA data processing are herein demonstrated in a pilot study of cases representing 50 sera from patients with malignant mesothelioma and a control sample of 65 sera from high risk subjects exposed to asbestos without symptoms of disease.