Advertisement

Glycoconjugate Journal

, Volume 25, Issue 1, pp 75–84 | Cite as

Serum antibody screening by surface plasmon resonance using a natural glycan microarray

  • Arjen R. de BoerEmail author
  • Cornelis H. Hokke
  • André M. Deelder
  • M. Wuhrer
Article

Abstract

A surface plasmon resonance (SPR) based natural glycan microarray was developed for screening of interactions between glycans and carbohydrate-binding proteins (CBPs). The microarray contained 144 glycan samples and allowed the real-time and simultaneous screening for recognition by CBPs without the need of fluorescent labeling. Glycans were released from their natural source and coupled by reductive amination with the fluorescent labels 2-aminobenzamide (2AB) or anthranilic acid (AA) followed by high-performance liquid chromatography (HPLC) fractionation making use of the fluorescent tag. The released and labeled glycans, in addition to fluorescently labeled synthetic glycans and (neo)glycoproteins, were printed on an epoxide-activated chip at fmol amounts. This resulted in covalent immobilization, with the epoxide groups forming covalent bonds to the secondary amine groups present on the fluorescent glycoconjugates. The generated SPR glycan array presented a subset of the glycan repertoire of the human parasite Schistosoma mansoni. In order to demonstrate the usefulness of the array in the simultaneous detection of glycan-specific serum antibodies, the anti-glycan antibody profiles from sera of S. mansoni-infected individuals as well as from non-endemic uninfected controls were recorded. The SPR screening was sensitive for differences between infection sera and control sera, and revealed antibody titers and antibody classes (IgG or IgM). All SPR analyses were performed with a single SPR array chip, which required regeneration and blocking of the chip before the application of a serum sample. Our results indicate that SPR-based arrays constructed from glycans of natural or synthetic origin, pure or as mixture, can be used for determining serum antibody profiles as possible markers for the infection status of an individual.

Keywords

Carbohydrate-binding protein detection Glycan microarray Natural glycans Serum screening Surface plasmon resonance 

Abbreviations

2AB

2-aminobenzamide

AA

anthranilic acid

CAA

circulating anodic antigen, -6)[GlcA(β1–3)]GalNAc(β1-

CBP

carbohydrate-binding protein

FGn

Fuc(α1–3)GlcNAc

FFGn

Fuc(α1–2)Fuc(α1–3)GlcNAc

FFFGn

Fuc(α1–2)Fuc(α1–2)Fuc(α1–3)GlcNAc

FLDN

Fuc(α1–3)GalNAc(β1–4)GlcNAc

FLDNF

Fuc(α1–3)GalNAc(β1–4)[Fuc(α1–3)]GlcNAc

HILIC

hydrophilic interaction liquid chromatography

HPLC

high-performance liquid chromatography

KLH

keyhole limpet hemocyanin

LDN

GalNAc(β1–4)GlcNAc

LDNF

GalNAc(β1–4)[Fuc(α1–3)]GlcNAc

LeX

Lewis X, Gal(β1–4)[Fuc(α1–3)]GlcNAc

MALDI-TOF-MS

matrix-assisted laser desorption/ionization-time of flight-mass spectrometry

PLSDA

partial least square for discriminant analysis

RP

reversed phase

SPR

surface plasmon resonance

Sm

Schistosoma mansoni

Notes

Acknowledgments

We would like to thank Carolien A.M. Koeleman for excellent technical assistance, and we appreciate the support of Dr. Marco R. Bladergroen, Dr. Alex A. Henneman, Dr. Alexandra van Remoortere, L. Renee Ruhaak and Dr. Govert J. van Dam. A. Sylvan, E. Verschuuren and P. Lidén (GE Healthcare) are gratefully acknowledged for help and cooperation. This study was supported by the Netherlands Genomics Initiative (Horizon Breakthrough Project 050-71-302) and GE Healthcare.

References

  1. 1.
    Blixt, O., Head, S., Mondala, T., Scanlan, C., Huflejt, M.E., Alvarez, R., Bryan, M.C., Fazio, F., Calarese, D., Stevens, J., Razi, N., Stevens, D.J., Skehel, J.J., van Die, I., Burton, D.R., Wilson, I.A., Cummings, R., Bovin, N., Wong, C.H., Paulson, J.C.: Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc. Natl. Acad. Sci. U. S. A. 101, 17033–17038 (2004)PubMedCrossRefGoogle Scholar
  2. 2.
    Feizi, T., Chai, W.G.: Oligosaccharide microarrays to decipher the glyco code. Nat. Rev. Mol. Cell Biol. 5, 582–588 (2004)PubMedCrossRefGoogle Scholar
  3. 3.
    Houseman, B.T., Mrksich, M.: Carbohydrate arrays for the evaluation of protein binding and enzymatic modification. Chem. Biol. 9, 443–454 (2002)PubMedCrossRefGoogle Scholar
  4. 4.
    Ratner, D.M., Adams, E.W., Disney, M.D., Seeberger, P.H.: Tools for glycomics: Mapping interactions of carbohydrates in biological systems. Chembiochem. 5, 1375–1383 (2004)PubMedCrossRefGoogle Scholar
  5. 5.
    Shilova, N.V., Galanina, O.E., Rubina, A.Y., Butvilovskaya, V.I., Huflejt, M.E., Chambers, J., Roucoux, A., Bovin, N.V.: 2-Aminopyridine—a label for bridging of oligosaccharides HPLC profiling and glycoarray printing. Glycoconj. J. (2007) this issueGoogle Scholar
  6. 6.
    Song, X., Xia, B., Lasanajak, Y., Smith, D.F., Cummings, R.D.: Quantifiable fluorescent glycan microarrays. Glycoconj. J. (2007) this issueGoogle Scholar
  7. 7.
    Xia, B.Y., Kawar, Z.S., Ju, T.Z., Alvarez, R.A., Sachdev, G.P., Cummings, R.D.: Versatile fluorescent derivatization of glycans for glycomic analysis. Nat. Methods. 2, 845–850 (2005)PubMedCrossRefGoogle Scholar
  8. 8.
    de Boer, A.R., Hokke, C.H., Deelder, A.M., Wuhrer, M.: General microarray technique for immobilization and screening of natural glycans. Anal. Chem. 79, 8107–8113 (2007)PubMedCrossRefGoogle Scholar
  9. 9.
    Blixt, O., Allin, K., Bohorov, O., Liu, X., Andersson-Sand, H., Hoffmann, J., Razi, N.: Glycan microarrays for screening sialyltransferase specificities. Glycoconj. J. (2007) this issueGoogle Scholar
  10. 10.
    Culf, A.S., Cuperlovic-Culf, M., Ouellette, R.J.: Carbohydrate microarrays: Survey of fabrication techniques. OMICS. 10, 289–310 (2006)PubMedCrossRefGoogle Scholar
  11. 11.
    Karamanska, R., Clarke, J., Blixt, O., MacRae, J.I., Zhang, J.Q., Crocker, P.R., Laurent, N., Wright, A., Flitsch, S.L., Russell, D.A., Field, R.A.: Surface plasmon resonance imaging for real-time, label-free analysis of protein interactions with carbohydrate microarrays. Glycoconj. J. (2007) this issueGoogle Scholar
  12. 12.
    Nibbeling, H.A.M., Kahama, A.I., Van Zeyl, R.J.M., Deelder, A.M.: Use of monoclonal antibodies prepared against Schistosoma mansoni hatching fluid antigens for demonstration of Schistosoma haematobium circulating egg antigens in urine. Am. J. Trop. Med. Hyg. 58, 543–550 (1998)PubMedGoogle Scholar
  13. 13.
    van Remoortere, A., Van Dam, G.J., Hokke, C.H., van den Eijnden, D.H., van Die, I., Deelder, A.M.: Profiles of immunoglobulin M (IgM) and IgG antibodies against defined carbohydrate epitopes in sera of Schistosoma-infected individuals determined by surface plasmon resonance. Infect. Immun. 69, 2396–2401 (2001)PubMedCrossRefGoogle Scholar
  14. 14.
    Bergwerff, A.A., Van Dam, G.J., Rotmans, J.P., Deelder, A.M., Kamerling, J.P., Vliegenthart, J.F.G.: The immunologically reactive part of immunopurified circulating anodic antigen from Schistosoma mansoni is a threonine-linked polysaccharide consisting of -6)-[b-D-GlcpA-(1–3)]-b-D-GalpNAc-(1- repeating units. J. Biol. Chem. 269, 31510–31517 (1994)PubMedGoogle Scholar
  15. 15.
    Vermeer, H.J., Van Dam, G.J., Halkes, K.M., Kamerling, J.P., Vliegenthart, J.F.G., Hokke, C.H., Deelder, A.M.: Immunodiagnostically applicable monoclonal antibodies to the circulating anodic antigen of Schistosoma mansoni bind to small, defined oligosaccharide epitopes. Parasitol. Res. 90, 330–336 (2003)PubMedCrossRefGoogle Scholar
  16. 16.
    van Roon, A.M., Aguilera, B., Cuenca, F., van, R.A., van der Marel, G.A., Deelder, A.M., Overkleeft, H.S., Hokke, C.H.: Synthesis and antibody-binding studies of a series of parasite fuco-oligosaccharides. Bioorg. Med. Chem. 13, 3553–3564 (2005)PubMedCrossRefGoogle Scholar
  17. 17.
    Wuhrer, M., Koeleman, C.A.M., Deelder, A.M., Hokke, C.H.: Repeats of LacdiNAc and fucosylated LacdiNAc on N-glycans of the human parasite Schistosoma mansoni. FEBS J. 273, 347–361 (2006)PubMedCrossRefGoogle Scholar
  18. 18.
    Wuhrer, M., Dennis, R.D., Doenhoff, M.J., Lochnit, G., Geyer, R.: Schistosoma mansoni cercarial glycolipids are dominated by Lewis X and pseudo-Lewis Y structures. Glycobiology. 10, 89–101 (2000)PubMedCrossRefGoogle Scholar
  19. 19.
    Folch, J., Lees, M., Stanley, G.H.S.: A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957)PubMedGoogle Scholar
  20. 20.
    Bigge, J.C., Patel, T.P., Bruce, J.A., Goulding, P.N., Charles, S.M., Parekh, R.B.: Nonselective and efficient fluorescent labeling of glycans using 2-amino benzamide and anthranilic acid. Anal. Biochem. 230, 229–238 (1995)PubMedCrossRefGoogle Scholar
  21. 21.
    Löfås, S., Johnsson, B.: A novel hydrogel matrix on gold surfaces in surface-plasmon resonance sensors for fast and efficient covalent immobilization of ligands. J. Chem. Soc. Chem. Commun. (21), 1526–1528 (1990)Google Scholar
  22. 22.
    Löfås, S.: Dextran modified self-assembled monolayer surfaces for use in biointeraction analysis with surface plasmon resonance. Pure Appl. Chem. 67, 829–834 (1995)CrossRefGoogle Scholar
  23. 23.
    Ro, H.S., Koh, B.H., Jung, S.O., Park, H.K., Shin, Y.B., Kim, M.G., Chung, B.H.: Surface plasmon resonance imaging protein arrays for analysis of triple protein interactions of HPV, E6, E6AP and p53. Proteomics. 6, 2108–2111 (2006)PubMedCrossRefGoogle Scholar
  24. 24.
    Anumula, K.R.: Advances in fluorescence derivatization methods for high-performance liquid chromatographic analysis of glycoprotein carbohydrates. Anal. Biochem. 350, 1–23 (2006)PubMedCrossRefGoogle Scholar
  25. 25.
    Shilova, N.V., Bovin, N.V.: Fluorescent labels for the analysis of mono- and oligosaccharides. Russ. J. Bioorg. Chem. 29, 309–324 (2003)CrossRefGoogle Scholar
  26. 26.
    Geyer, H., Wuhrer, M., Resemann, A., Geyer, R.: Identification and characterization of keyhole limpet hemocyanin N-glycans mediating cross-reactivity with Schistosoma mansoni. J. Biol. Chem. 280, 40731–40748 (2005)PubMedCrossRefGoogle Scholar
  27. 27.
    Domon, B., Costello, C.E.: A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconj. J. 5, 397–409 (1988)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Arjen R. de Boer
    • 1
    Email author
  • Cornelis H. Hokke
    • 1
  • André M. Deelder
    • 1
  • M. Wuhrer
    • 1
  1. 1.Biomolecular Mass Spectrometry Unit, Department of Parasitology, Center of Infectious DiseasesLeiden University Medical CenterRC LeidenThe Netherlands

Personalised recommendations