Abstract
The fixed constant (Fc) region of IgG is subject to changes in glycosylation state in response to diseases. On the basis of sera from 75 healthy controls, 75 pancreatitis (PT) patients, and 75 pancreatic adenocarcinoma (PAC) patients, we analyzed six fucosylated glycoforms of IgG2 (G0F, G1F, G2F, G0FN, G1FN, and G2FN), by matrix-assisted laser desorption/ionization–Fourier-transform ion cyclotron resonance mass spectrometry (MALDI–FTICR MS), to evaluate their use as biomarkers for pancreatic diseases. Compared with healthy controls, significant increases in agalactosylated glycoforms and decreases in galactosylated glycoforms were observed for PT and PAC patients. Logistic regression analysis suggested that truncation of the sugar chain was prone to occur in PT and, especially, PAC patients. After participants were stratified by sex and age, receiver operating characteristic curve analysis revealed good overall sensitivity and specificity for discrimination of PAC and PT patients from healthy controls. A combination of G0F and galactosylation also had acceptable power for differentiating PAC patients from PT patients.
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Abbreviations
- ANOVA:
-
One-way analysis of variance
- AUC:
-
Area under receiver operating characteristic curve
- MALDI–FTICR MS:
-
Matrix-assisted laser desorption/ionization–Fourier-transform ion cyclotron resonance mass spectrometry
- MS:
-
Mass spectrometry
- PAC:
-
Pancreatic adenocarcinoma
- PT:
-
Pancreatitis
- ROC:
-
Receiver operating characteristic
References
Arnold JN, Wormald MR, Sim RB, Rudd PM, Dwek RA (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25:21–50
Chan AC, Carter PJ (2010) Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 10:301–316
Hodoniczky J, Zheng YZ, James DC (2005) Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro. Biotechnol Prog 21:1644–1652
Umana P, Jean-Mairet J, Moudry R, Amstutz H, Bailey JE (1999) Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. Nat Biotechnol 17:176–180
Jemal A, Bray F, Center MM, Ferlay J, Ward E et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG et al (1993) Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med 328:1433–1437
Farrow B, Evers BM (2002) Inflammation and the development of pancreatic cancer. Surg Oncol 10:153–169
Chen G, Wang Y, Qiu L, Qin X, Liu H et al (2012) Human IgG Fc-glycosylation profiling reveals associations with age, sex, female sex hormones and thyroid cancer. J Proteomics 75:2824–2834
Selman MH, McDonnell LA, Palmblad M, Ruhaak LR, Deelder AM et al (2010) Immunoglobulin G glycopeptide profiling by matrix-assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem 82:1073–1081
Nouts A, Levy P, Voitot H, Bernades P (1998) Diagnostic value of serum Ca 19–9 antigen in chronic pancreatitis and pancreatic adenocarcinoma. Gastroenterol Clin Biol 22:152–159
Acknowledgments
This study was supported by grant no. 21075137 from the National Natural Science Foundation of China and by the Research Fund for the Doctoral Program of Higher Education (grant no. 20121106110023) (to Z. Li).
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Chen, G., Li, H., Qiu, L. et al. Change of fucosylated IgG2 Fc-glycoforms in pancreatitis and pancreatic adenocarcinoma: a promising disease-classification model. Anal Bioanal Chem 406, 267–273 (2014). https://doi.org/10.1007/s00216-013-7439-3
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DOI: https://doi.org/10.1007/s00216-013-7439-3