Dataset Information

IgA deglycosylation to identify glycosylation sites

ABSTRACT: In order to provide information on the peptide sequence of the IgA glycopeptides, a proteomics analysis was run on LC-MS/MS data of N-glycosidase F-digested IgA samples, in which the N-glycans had been released. The samples included IgA (isolated) from: 1) the saliva samples from two healthy donors, 2) a pooled-plasma standard from a minimum of 20 human donors (VisuCon-F Frozen Normal Control Plasma; Affinity Biologicals, Ancaster, Canada), 3) 10 μg of a human plasma-derived IgA standard (Lee Biosolutions, Maryland Heights, MO), and 4) a human colostrum-derived SIgA standard (Athens Research and Technology, Athens, GA).

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma, Colostrum, Saliva

SUBMITTER: Noortje de Haan

LAB HEAD: Manfred Wuhrer

PROVIDER: PXD011228 | Pride | 2018-11-09

REPOSITORIES: Pride

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Publications

Comparative Glycomics of Immunoglobulin A and G From Saliva and Plasma Reveals Biomarker Potential.

Plomp Rosina R de Haan Noortje N Bondt Albert A Murli Jayshri J Dotz Viktoria V Wuhrer Manfred M

Frontiers in immunology 20181023

The <i>N</i>-glycosylation of immunoglobulin (Ig) G, the major antibody in the circulation of human adults, is well known for its influence on antibody effector functions and its alterations with various diseases. In contrast, knowledge on the role of glycans attached to IgA, which is a key immune defense agent in secretions, is very scarce. In this study we aimed to characterize the glycosylation of salivary (secretory) IgA, including the IgA joining chain (JC), and secretory component (SC) and ...[more]

PMID: 30405629

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Project description:Desmoid tumors (also called deep or aggressive fibromatoses) are potentially life-threatening fibromatous lesions. Hereditary desmoid tumors arise in individuals affected by either familial adenomatous polyposis (FAP) or hereditary desmoid disease (HDD) carrying germline mutations in APC. Most non-FAP (sporadic) desmoids carry somatic mutations in the beta-catenin gene. Previous studies identified losses on 5q and 6q, and gains on 8q and 20q as recurrent genetic changes in desmoids. However, virtually all genetic changes were derived from sporadic tumors. To investigate the somatic alterations in FAP-associated desmoids and to compare them with changes occurring in sporadic tumors, we analyzed 17 FAP-associated and 38 sporadic desmoids for copy number abnormalities (CNAs) by means of array comparative genomic hybridization and multiple ligation-dependent probe amplification. Overall, the desmoids displayed only a limited number of genetic changes, occurring in 44% of cases. Common gains at 8q (7%) and 20q (5%) were almost exclusively found in sporadic tumors. Frequent common losses were observed within a 700 kb region at 5q22.2, comprising the APC gene (11%), in a 2 Mb region at 6p21.2-p21.1 (15%), and in a relatively large region at 6q15-q23.3 (20%). The FAP-associated desmoids displayed a significantly higher frequency of CNAs (59%) than the sporadic tumors (37%). As predicted by the APC germline mutations among these patients, a relatively high percentage (29%) of the FAP-associated desmoids showed loss of the APC region at 5q22.2, which was infrequently (3%) seen among sporadic tumors. Our data suggest that loss of region 6q15-q16.2 is an important event in FAP-associated as well as sporadic desmoids, most likely of relevance for desmoid tumor progression. Fifty-three fresh frozen tumor samples were collected at four institutes: Center for Human Genetics, University of Leuven, Belgium (21 samples); INSERM U674, Fondation Jean Dausset-CEPH, Paris, France (15 samples); Hospital for Sick Children, Toronto, Canada (13 samples); and the Italian Registry of Hereditary Colorectal Cancer (Dr. L. Bertario, 4 samples). In addition, DNA of two fresh frozen tumors, HDD-H of patient III:2 and HDD-I of patient III:6, of our hereditary desmoids disease (HDD) family10 was available (Table 1). In this family, multifocal desmoid tumors were inherited as an autosomal dominant trait, and HDD segregated with a 3' APC mutation at codon 1924. For the latter reason, they were classified as FAP tumors in this study. Three FAP tumors were derived from a family with 2 relatives in the study (D15-1 and D15-2 of a male patient and D16 of his sister). Colonic polyposis had been observed in 12 FAP patients, not in the 2 HDD-FAP patients and not in patient D15. The germline APC mutation was known in 14 of 17 FAP-associated tumors. In 28 of 38 non-FAP-associated desmoid tumors, the beta-catenin gene (CTNNB1) mutation in exon 3 was known and in 1 of 38 tumors an APC mutation was present (data not shown). The remaining tumors were characterized as FAP or non-FAP based on clinical data and positivity of tumor cells upon immunostaining for beta-catenin. DNA was extracted from the tumor samples according to standard methods.

Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his baseline serum anti-glycan antibody levels. Results: Pre-vaccination antibody levels to blood group A trisaccharide (BG-Atri) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with abundant anti-BG-Atri IgM relative to subjects with little or no pre-existing IgM for BG-Atri. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-BG-Atri IgM levels were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new potentially predictive biomarker for PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). Total immunoglobin (IgM + IgG + IgA) levels for the training set measured at serum dilution of 1:50 are detailed here. The screen for predictive biomarkers identified anti-glycan antibodies that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Due to the potential for overfitting, a permutation test was used to estimate the false discovery rate. Raw data on superSeries GSE42184 record.

Dataset Information

IgA deglycosylation to identify glycosylation sites

Publications

Comparative Glycomics of Immunoglobulin A and G From Saliva and Plasma Reveals Biomarker Potential.

Similar Datasets

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