Skip to main content

Advertisement

Log in

An integrated proteomic and glycoproteomic study for differences on glycosylation occupancy in rheumatoid arthritis

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease in which certain immune cells are dysfunctional and attack their own healthy tissues. There has been great difficulty in finding an accurate and efficient method for the diagnosis of early-stage RA. The present shortage of diagnostic methods leads to the rough treatments of the patients in the late stages, such as joint removing. Nowadays, there is an increasing focus on glyco-biomarkers discovery for malicious disease via MS-based strategy. In this study, we present an integrated proteomics and glycoproteomics approach to uncover the pathological changes of some RA-related glyco-biomarkers and glyco-checkpoints involved in the RA onset. Among 39 distinctly expressive N-glycoproteins, 27 N-glycoproteins were discovered with over twofold expression significances. On the other hand, 13 proteins have been distinguished with significant differences in 53 distinctly expressed proteins identified in this study. Such an integrated approach will provide a comprehensive strategy for new potential glyco-biomarkers and checkpoints discovery in rheumatoid arthritis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Scott DL, Wolfe F, Huizinga WJH. Rheumatoid arthritis. Lancet. 2010;376:1094–108.

    Article  PubMed  Google Scholar 

  2. Klareskog L, Padyukov L, Lorentzen J, Alfredsson L. Mechanisms of disease: genetic susceptibility and environmental triggers in the development of rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006;2(8):425–33.

    Article  CAS  PubMed  Google Scholar 

  3. Lindstrom TM, Robinson WH. Biomarkers for rheumatoid arthritis: making it personal. Scand J Clin Lab Investig Suppl. 2010;242:79–84.

    Article  Google Scholar 

  4. Snir O, Widhe M, von Spee C, Lindberg J, Padyukov L, Lundberg K, et al. Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: association with HLA-DRB1 alleles. Ann Rheum Dis. 2009;68(5):736–43.

    Article  CAS  PubMed  Google Scholar 

  5. Burska A, Boissinot M, Ponchel F. Cytokines as biomarkers in rheumatoid arthritis. Mediat Inflamm. 2014;2014:545493.

    Google Scholar 

  6. Chard MD, Calvin J, Price CP, Cawston TE, Hazleman BL. Serum alpha 1 antichymotrypsin concentration as a marker of disease activity in rheumatoid arthritis. Ann Rheum Dis. 1988;47(8):665–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ha YJ, Kang EJ, Lee SW, Lee SK, Park YB, Song JS, et al. Usefulness of serum leucine-rich alpha-2 glycoprotein as a disease activity biomarker in patients with rheumatoid arthritis. J Korean Med Sci. 2014;29(9):1199–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhao J, Simeone DM, Heidt D, Anderson MA, Lubman DM. Comparative serum glycoproteomics using lectin selected sialic acid glycoproteins with mass spectrometric analysis: application to pancreatic cancer serum. J Proteome Res. 2006;5(7):1792–802.

    Article  CAS  PubMed  Google Scholar 

  9. Varki ACR, Esko J, Freeze H, Hart G, Marth J. Essentials of glycobiology. New York: Cold spring harbor laboratory press; 1999.

    Google Scholar 

  10. Stevens J, Spang A. N-glycosylation is required for secretion and mitosis in C. elegans. PLoS One. 2013;8(5):e63687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hart GW, Copeland RJ. Glycomics hits the big time. Cell. 2010;143(5):672–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Huang Y, Wu H, Xue R, Liu T, Dong L, Yao J, et al. Identification of N-glycosylation in hepatocellular carcinoma patients’ serum with a comparative proteomic approach. PLoS One. 2013;8(10):e77161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Saldova R, Royle L, Radcliffe CM, Abd Hamid UM, Evans R, Arnold JN, et al. Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG. Glycobiology. 2007;17(12):1344–56.

    Article  CAS  PubMed  Google Scholar 

  14. Vasseur JA, Goetz JA, Alley WR Jr, Novotny MV. Smoking and lung cancer-induced changes in N-glycosylation of blood serum proteins. Glycobiology. 2012;22(12):1684–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yoon SJ, Park SY, Pang PC, Gallagher J, Gottesman JE, Dell A, et al. N-glycosylation status of beta-haptoglobin in sera of patients with prostate cancer vs. benign prostate diseases. Int J Oncol. 2010;36(1):193–203.

    CAS  PubMed  Google Scholar 

  16. Dennis JW, Granovsky M, Warren CE. Protein glycosylation in development and disease. BioEssays. 1999;21(5):412–21.

    Article  CAS  PubMed  Google Scholar 

  17. Lowe JB. Glycan-dependent leukocyte adhesion and recruitment in inflammation. Curr Opin Cell Biol. 2003;15(5):531–8.

    Article  CAS  PubMed  Google Scholar 

  18. Mechref Y, Hu Y, Garcia A, Hussein A. Identifying cancer biomarkers by mass spectrometry-based glycomics. Electrophoresis. 2012;33(12):1755–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kirwan A, Utratna M, O'Dwyer ME, Joshi L, Kilcoyne M. Glycosylation-based serum biomarkers for cancer diagnostics and prognostics. Biomed Res Int. 2015;2015:490531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yang L, Zou QH, Zhang Y, Shi Y, Hu CR, Hui CX, et al. Proteomic analysis of plasma from rheumatoid arthritis patients with mild cognitive impairment. Clin Rheumatol. 2018;37(7):1773–82.

    Article  PubMed  Google Scholar 

  21. Reiding KR, Vreeker G, Bondt A, Bladergroen MR, Hazes JM, van der Burgt YE, et al. Serum protein N-glycosylation changes with rheumatoid arthritis disease activity during and after pregnancy. Front Med (Lausanne). 2017;4:241.

    Article  Google Scholar 

  22. Marth JD, Grewal PK. Mammalian glycosylation in immunity. Nat Rev Immunol. 2008;8(11):874–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wisniewski JR, Zougman A, Mann M. Combination of FASP and StageTip-based fractionation allows in-depth analysis of the hippocampal membrane proteome. J Proteome Res. 2009;8(12):5674–8.

    Article  CAS  PubMed  Google Scholar 

  24. Ma C, Zhao X, Han H, Tong W, Zhang Q, Qin P, et al. N-linked glycoproteome profiling of human serum using tandem enrichment and multiple fraction concatenation. Electrophoresis. 2013;34(16):2440–50.

    Article  CAS  PubMed  Google Scholar 

  25. Wang LH, Li DQ, Fu Y, Wang HP, Zhang JF, Yuan ZF, et al. pFind 2.0: a software package for peptide and protein identification via tandem mass spectrometry. Rapid Commun Mass Spectrom. 2007;21(18):2985–91.

    Article  CAS  PubMed  Google Scholar 

  26. Malovannaya A, Lanz RB, Jung SY, Bulynko Y, Le NT, Chan DW, et al. Analysis of the human endogenous coregulator complexome. Cell. 2011;145(5):787–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang Z, Bast RC Jr, Yu Y, Li J, Sokoll LJ, Rai AJ, et al. Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res. 2004;64:5882–90.

    Article  CAS  PubMed  Google Scholar 

  28. Kim EY, Lee MY, Kim SH, Ha K, Kim KP, Ahn YM. Diagnosis of major depressive disorder by combining multimodal information from heart rate dynamics and serum proteomics using machine-learning algorithm. Prog Neuro-Psychopharmacol Biol Psychiatry. 2017;76:65–71.

    Article  CAS  Google Scholar 

  29. Shiromizu T, Kume H, Ishida M, Adachi J, Kano M, Matsubara H, et al. Quantitation of putative colorectal cancer biomarker candidates in serum extracellular vesicles by targeted proteomics. Sci Rep. 2017;7(1):12782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Barker PE, Wagner PD, Stein SE, Bunk DM, Srivastava S, Omenn GS. Standards for plasma and serum proteomics in early cancer detection: a needs assessment report from the national institute of standards and technology--National Cancer Institute standards, methods, assays, reagents and technologies workshop, August 18-19, 2005. Clin Chem. 2006;52(9):1669–74.

    Article  CAS  PubMed  Google Scholar 

  31. Crowgey EL, Wyffels JT, Osborn PM, Wood TT, Edsberg LE. A systems biology approach for studying heterotopic ossification: proteomic analysis of clinical serum and tissue samples. Genomics Proteomics Bioinformatics. 2018;16(3):212–20.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wisniewski JR. Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. Proteomics. 2004;4(2):454–65.

    Article  CAS  PubMed  Google Scholar 

  33. Kolarich D, Weber A, Turecek PL, Schwarz HP, Altmann F. Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge isoforms. Proteomics. 2006;6(11):3369–80.

    Article  CAS  PubMed  Google Scholar 

  34. Liang Y, Ma T, Thakur A, Yu H, Gao L, Shi P, et al. Differentially expressed glycosylated patterns of alpha-1-antitrypsin as serum biomarkers for the diagnosis of lung cancer. Glycobiology. 2015;25(3):331–40.

    Article  CAS  PubMed  Google Scholar 

  35. Topic A, Ljujic M, Radojkovic D. Alpha-1-antitrypsin in pathogenesis of hepatocellular carcinoma. Hepat Mon. 2012;12(10 HCC):e7042.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Chrostek L, Cylwik B, Gindzienska-Sieskiewicz E, Gruszewska E, Szmitkowski M, Sierakowski S. Sialic acid level reflects the disturbances of glycosylation and acute-phase reaction in rheumatic diseases. Rheumatol Int. 2014;34(3):393–9.

    Article  CAS  PubMed  Google Scholar 

  37. McCarthy C, Saldova R, Wormald MR, Rudd PM, McElvaney NG, Reeves EP. The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions. J Proteome Res. 2014;13(7):3131–43.

    Article  CAS  PubMed  Google Scholar 

  38. Sarrats A, Saldova R, Pla E, Fort E, Harvey DJ, Struwe WB, et al. Glycosylation of liver acute-phase proteins in pancreatic cancer and chronic pancreatitis. Proteomics Clin Appl. 2010;4(4):432–48.

    Article  CAS  PubMed  Google Scholar 

  39. Zhao J, Fan YX, Yang Y, Liu DL, Wu K, Wen FB, et al. Identification of potential plasma biomarkers for esophageal squamous cell carcinoma by a proteomic method. Int J Clin Exp Pathol. 2015;8(2):1535–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, et al. Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009;8(2):651–61.

    Article  CAS  PubMed  Google Scholar 

  41. Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, et al. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005;4(6):2070–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. The complement system and innate immunity. Immunobiology: the immune system in health and disease. 5th ed. New York: Garland Science; 2001.

    Google Scholar 

  43. Wouters D, Voskuyl AE, Molenaar ET, Dijkmans BA, Hack CE. Evaluation of classical complement pathway activation in rheumatoid arthritis: measurement of C1q-C4 complexes as novel activation products. Arthritis Rheum. 2006;54(4):1143–50.

    Article  CAS  PubMed  Google Scholar 

  44. Ritchie GE, Moffatt BE, Sim RB, Morgan BP, Dwek RA, Rudd PM. Glycosylation and the complement system. Chem Rev. 2002;102(2):305-20-19.

    Article  CAS  PubMed  Google Scholar 

  45. Ji H, Ohmura K, Mahmood U, Lee DM, Hofhuis FM, Boackle SA, et al. Arthritis critically dependent on innate immune system players. Immunity. 2002;16(2):157–68.

    Article  CAS  PubMed  Google Scholar 

  46. Ballanti E, Perricone C, di Muzio G, Kroegler B, Chimenti MS, Graceffa D, et al. Role of the complement system in rheumatoid arthritis and psoriatic arthritis: relationship with anti-TNF inhibitors. Autoimmun Rev. 2011;10(10):617–23.

    Article  CAS  PubMed  Google Scholar 

  47. de Córdoba SR, Esparza-Gordillo J, de Jorge EG, Lopez-Trascasa M, Sánchez-Corral P. The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol. 2004;41(4):355–67.

    Article  CAS  Google Scholar 

  48. Stanley KK, Kocher HP, Luzio JP, Jackson P, Tschopp J. The sequence and topology of human complement component C9. EMBO J. 1985;4(2):375–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We sincerely thank Georgia Research Alliance (GRA) and Georgia State University for purchasing the analytical instrument used in this research.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Peng George Wang or Cheng Ma.

Ethics declarations

The study was approved by the Ethics Committee of Peking University People’s Hospital (Approval No. 2015 PHB 219-01). All participants of this study provided informed consent for participation in this study.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 173 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Ding, L., Li, X. et al. An integrated proteomic and glycoproteomic study for differences on glycosylation occupancy in rheumatoid arthritis. Anal Bioanal Chem 411, 1331–1338 (2019). https://doi.org/10.1007/s00216-018-1543-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-018-1543-3

Keywords

Navigation