Detection of altered N-glycan profiles in whole serum from rheumatoid arthritis patients

Nakagawa, Hiroaki; Hato, Masakatsu; Takegawa, Yasuhiro; Deguchi, Kisaburo; Ito, Hiroki; Takahata, Masahiko; Iwasaki, Norimasa; Minami, Akio; Nishimura, Shin‐Ichiro

doi:10.1016/j.jchromb.2007.03.003

Cited by 39 publications

(27 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study demonstrated the detailed structures including the linkage information and the abundance changes of sialylated glycans in RA serum. The differences of specific glycans and the significant increase of tri- and tetra-sialylated glycoforms as well as fucosylation was consistent with previous works [27]. These observed changes of glycosylation demonstrate the possibility of using glycans as biomarker for RA diagnosis in the future.…”

Section: Resultssupporting

confidence: 91%

“…Aberrant glycosylation happens on several important serum glycoproteins, such as IgG, haptoglobin (Hp), and alpha-1-acid glycoprotein (AGP) in RA patients [24–26]. Previous studies investigated the N-glycan patterns in the serum of RA patients [27–29]. However, the comparison of glycans between RA patients and healthy controls in detail has not yet been investigated, since the isomeric glycans were difficult to be identified and annotated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sialic acid linkage-specific permethylation for improved profiling of protein glycosylation by MALDI-TOF MS

Jiang

Zhu

et al. 2017

Analytica Chimica Acta

View full text Add to dashboard Cite

Protein glycosylation mediates a wide range of cellular processes, affecting development and disease in mammals. Deciphering the “glycocodes” requires rapid, sensitive and in-depth characterization of diverse glycan structures derived from biological samples. In this study, we described a two-step derivatization strategy termed linkage-specific sialic acid permethylation (SSAP) consisting of dimethylamination and permethylation for the improved profiling of glycosylation by matrix-assisted laser desorption/ionization (MALDI) time-of-fight (TOF) mass spectrometry (MS). High linkage-specificity (~99%) of SSAP to both the two most common forms of sialic acid, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), permitting direct discrimination of α2,3- and α2,6-linked sialic acids in MALDI-TOF MS. The enhanced intensity (>10-fold) and increased detection limit (>10-fold) of derivatized glycans were valued for sensitive glycomics. Moreover, the good compatibility and reaction efficiency of the two steps of SSAP allowed rapid sample preparation (<2 h), benefiting robust analysis of glycans in a high-throughput manner. The SSAP strategy was further applied to investigate the protein glycosylation of human serum associated with rheumatoid arthritis (RA). It was demonstrated that the relative abundances of individual glycans were different in RA negative and RA positive samples, and meanwhile the RA patient/control ratios of both α2,3- and α2,6-sialylated glycans tended to elevate accompanied with the increase of sialylation. Those findings of the glycosylation changes occurred in human serum protein may contribute to the diagnosis of RA. Herein, SSAP derivatization combined with MALDI-TOF MS exhibits unique advantages for glycomic analysis and shows potential in glycosylation profiling of therapeutic proteins and clinical glycan biomarker discovery.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Sialic acid linkage-specific permethylation for improved profiling of protein glycosylation by MALDI-TOF MS

Jiang

Zhu

et al. 2017

Analytica Chimica Acta

View full text Add to dashboard Cite

show abstract

“…Nakagawa et al employed a more traditional reversed phase LC/MS-based approach to analyze N-glycan isomers from rheumatoid arthritis patients; however, glycans had to be desialylated and then derivatized prior to analysis. 26 Bones et al attempted a non-MS approach involving ultra performance LC and fluorescence detection of labeled N-glycans. 27 In contrast, Prien et al employed a wholly non-chromatographic approach using MS n to differentiate structural isomers for a small number of derivatized glycans isolated from tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive native glycan profiling with isomer separation and quantitation for the discovery of cancer biomarkers

Hua

Özcan

et al. 2011

Analyst

145

179

View full text Add to dashboard Cite

Glycosylation is highly sensitive to the biochemical environment and has been implicated in many diseases including cancer. Glycan compositional profiling of human serum with mass spectrometry has already identified potential biomarkers for several types of cancer and diseases; however, composition alone does not fully describe glycan stereo- and regioisomeric diversity. The vast structural heterogeneity of glycans presents a formidable analytical challenge. We have developed a method to identify and quantify isomeric native glycans using nanoflow liquid chromatography (nano-LC)/mass spectrometry. A microfluidic chip packed with graphitized carbon was used to chromatographically separate the glycans. To determine the utility of this method for structure-specific biomarker discovery, we analyzed serum samples from two groups of prostate cancer patients with different prognoses. More than 300 N-glycan species (including isomeric structures) were identified, corresponding to over 100 N-glycan compositions. Statistical tests established significant differences in glycan abundances between patient groups. This method provides comprehensive, selective, and quantitative glycan profiling.

show abstract

“…Alterations in glycans in cancer cells were shown and linked with cell adhesion, metastasis, and oncogenic transformation, and those in the endothelium of inflammation tissue were shown and linked with leukocyte homing (9). Moreover, the structural changes in the N-glycan of serum proteins are associated with some diseases, e.g., agalactosylation (35) and fucosylation (14) of IgG in rheumatoid arthritis (32) and ␣1,6-fucosylation of ␣-fetoprotein in hepatocellular carcinoma (3,4). Those are suggested to be useful for clinical markers (2).…”

mentioning

confidence: 99%

Analysis ofN-glycan in serum glycoproteins fromdb/dbmice and humans with type 2 diabetes

Itoh¹,

Sakaue²,

Nakagawa³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

Glycosylation has an important role in regulating properties of proteins and is associated with many diseases. To examine the alteration of serum N-glycans in type 2 diabetes, we used the db/db mouse model. Serum N-glycans were fluorescence labeled and applied to HPLC. There were reproducible differences in N-glycan profiles between the db/db mouse model and the db/+ control. The structures of the oligosaccharides, which had changed in their amounts, were analyzed by a two-dimensional mapping method, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, and exoglycosidase digestion. Those analyses revealed an increase in the N-glycans possessing α1,6-fucose in the serum of db/db mice. The level of α1,6-fucosyltransferase mRNA was increased in the liver of the db/db mice. The ratio of a biantennary N-glycan with α1,6-fucose to that without α1,6-fucose in the liver tissue of the db/db mouse was increased relative to the db/+ control. Next, we analyzed the serum N-glycan profile in human subjects with type 2 diabetes and found an increased amount of a biantennary N-glycan that had an α1,6-fucose with a bisecting N-acetylglucosamine. In conclusion, the increase in α1,6-fucosylation is a striking change in the serum N-glycans of the db/db mice, whereas the change in the fucosylation in humans with type 2 diabetes was small, albeit statistically significant. It is likely that the change is caused, at least partially, by the increase in the α1,6-fucosyltransferase mRNA level in the liver. The increased α1,6-fucosylation may affect protein properties associated with the pathophysiology of type 2 diabetes.

show abstract

Detection of altered N-glycan profiles in whole serum from rheumatoid arthritis patients

Cited by 39 publications

References 26 publications

Sialic acid linkage-specific permethylation for improved profiling of protein glycosylation by MALDI-TOF MS

Sialic acid linkage-specific permethylation for improved profiling of protein glycosylation by MALDI-TOF MS

Comprehensive native glycan profiling with isomer separation and quantitation for the discovery of cancer biomarkers

Analysis ofN-glycan in serum glycoproteins fromdb/dbmice and humans with type 2 diabetes

Contact Info

Product

Resources

About