Skip to main content
SpringerLink
Log in

Natural antibodies to glycans

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

A wide variety of so-called natural antibodies (nAbs), i.e. immunoglobulins generated by B-1 cells, are directed to glycans. nAbs to glycans can be divided in three groups: 1) conservative nAbs, i.e. practically the same in all healthy donors with respect to their epitope specificity and level in blood; 2) allo-antibodies to blood group antigens; 3) plastic antibodies related to the first or the second group but discussed separately because their level changes considerably during diseases and some temporary conditions, in particular inflammation and pregnancy. Antibodies from the third group proved to be prospective markers of a number of diseases, whereas their unusual level (below or above the norm) is not necessarily the consequence of disease/state. Modern microarrays allowed the determination of the human repertoire, which proved to be unexpectedly broad. It was observed that the content of some nAbs reaches about 0.1% of total immunoglobulins. Immunoglobulins of M class dominate for most nAbs, constituting up to 80-90%. Their affinity (to a monovalent glycan, in K D terms) was found to be within the range 10−4–10−6 M. Antibodies to Galβ1-3GlcNAc (LeC), 4-HSO3Galβ1-4GalNAc (4′-O-SuLN), Fucα1-3GlcNAc, Fucα1-4GlcNAc, GalNAcα1-3Gal (Adi), Galα1-4Galβ1-4Glc (Pk), Galα1-4Galβ1-4GlcNAc (P1), GlcNAcα-terminated glycans, and hyaluronic acid should be noted among the nAbs revealed and studied during the last decade. At the same time, a kind of “taboo” is observed for a number of glycans: antibodies to LeX and LeY, and almost all gangliosides have not been observed in healthy persons. Many of the revealed nAbs were directed to constrained inner (core) part of glycan, directly adjoined to lipid of cell membrane or protein. The biological function of these nAbs remains unclear; for anti-core antibodies, a role of surveillance on appearance of aberrant, especially cancer, antigens is supposed. The first data related to oncodiagnostics based on quantitation of anti-glycan nAbs are reported.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ELISA:

enzyme-linked immunosorbent assay

Ig:

immunoglobulin

nAbs:

natural antibodies

PGA:

printed glycan array

SA:

suspension array

Sia:

sialic acid residue

Su:

sulfate

TACA:

tumor-associated carbohydrate antigen

References

  1. George, J., and Shoenfeld, Y. (1996) in Autoantibodies (Peter, J. B., and Shoenfeld, Y., eds.) Elsevier, pp. 534–539.

  2. Kaveri, S. V., Silverman, G. J., and Bayry, J. (2012) J. Immunol., 188, 939–945.

    Article  PubMed  CAS  Google Scholar 

  3. Avrameas, S. (1991) Immunol. Today, 12, 154–159.

    PubMed  CAS  Google Scholar 

  4. Galanina, O. E., Mecklenburg, M., Nifantiev, N. E., Pazynina, G. V., and Bovin, N. V. (2003) Lab. Chip, 3, 260–265.

    Article  PubMed  CAS  Google Scholar 

  5. 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., and Paulson, J. C. (2004) Proc. Natl. Acad. Sci. USA, 101, 17033–17038.

    Article  PubMed  CAS  Google Scholar 

  6. Pochechueva, T., Jacob, F., Goldstein, D. R., Huflejt, M. E., Chinarev, A., Caduff, R., Fink, D., Hacker, N., Bovin, N. V., and Heinzelmann-Schwarz, V. (2011) Glycoconj. J., 8–9, 507–517; PMID: 21948103.

    Article  Google Scholar 

  7. Alvarez, R. A., and Blixt, O. (2006) Methods Enzymol., 415, 292–310.

    Article  PubMed  CAS  Google Scholar 

  8. Shilova, N. V., Navakouski, M. J., Huflejt, M., Kuehn, A., Grunow, R., Blixt, O., and Bovin, N. V. (2011) Biochemistry (Moscow), 76, 862–866.

    Article  CAS  Google Scholar 

  9. The Functional Glycomics Gateway, www.functionalglycomics.org

  10. Park, S., Gildersleeve, J. C., Blixt, O., and Shin, I. (2013) Chem. Soc. Rev., DOI: 10.1039/C2CS35401B.

    Google Scholar 

  11. Tupitsyn, N. N., Udalova, Y. A., Galanina, O. E., Kadagidze, Z. G., Borovkova, N. B., Podolsky, V. V., Shinkarev, S. A., Gadetskaya, N. A., Letyagin, V. P., Obukhova, P. S., Shilova, N. V., Subbotina, A. A., and Bovin, N. V. (2009) Hematopoiesis Immunol., 2, 45–54.

    Google Scholar 

  12. Obukhova, P., Piskarev, V., Severov, V., Pazynina, G., Tuzikov, A., Navakouski, M., Shilova, N., and Bovin, N. (2011) Glycoconj. J., 8–9, 501–505; PMID: 22057658.

    Article  Google Scholar 

  13. Obukhova, P., Korchagina, E., Henry, S., and Bovin, N. (2011) Transfusion, 52, 860–869; PMID: 21981750.

    Article  PubMed  Google Scholar 

  14. Obukhova, P., Rieben, R., and Bovin, N. (2007) Xenotransplantation, 14, 627–635.

    Article  PubMed  Google Scholar 

  15. Korchagina, E. Y., Pochechueva, T. V., Obukhova, P. S., Formanovsky, A. A., Imberty, A., Rieben, R., and Bovin, N. V. (2005) Glycoconj. J., 22, 127–133.

    Article  PubMed  CAS  Google Scholar 

  16. Smorodin, E. P., Jansson, B., Milyukhina, L., Paaski, G., Bovin, N. V., Ovchinnikova, T. V., and Kurtenkov, O. (1997) Rus. J. Bioorg. Chem., 23, 718–721.

    Google Scholar 

  17. Huflejt, M. E., Vuskovic, M., Vasiliu, D., Xu, H., Obukhova, P., Shilova, N., Tuzikov, A., Galanina, O., Arun, B., Lu, K., and Bovin, N. (2009) Mol. Immunol., 46, 3037–3049.

    Article  PubMed  CAS  Google Scholar 

  18. Frete, D., Srivastava, V., Hindsgaul, O., and Baenziger, J. U. (1991) Cell, 67, 1103–1110.

    Article  Google Scholar 

  19. Grader-Beck, T., Boin, F., von Gunten, S., Smith, D., Rosen, A., and Bochner, B. S. (2011) Ann. Rheum. Dis., 70, 2218–2224.

    Article  PubMed  Google Scholar 

  20. Bovin, N., Obukhova, P., Shilova, N., Rapoport, E., Popova, I., Navakouski, M., Unverzagt, C., Vuskovic, M., and Huflejt, M. (2012) Biochim. Biophys. Acta, Gen. Subj., 1820, 1373–1382; DOI: 10.1016/j.bbagen.2012.02.005.

    Article  CAS  Google Scholar 

  21. Ishihara, K., Kurihara, M., Goso, Y., Urata, T., Ota, H., Katsuyama, T., and Hotta, K. (1996) Biochem. J., 318, 409–416.

    PubMed  CAS  Google Scholar 

  22. Svensson, L., Hult, A. K., Stamps, R., Angstrom, J., Teneberg, S., Storry, J. R., Jorgensen, R., Rydberg, L., Henry, S. M., and Olsson, M. L. (2012) Blood, Published ahead of print December 18, 2012, doi: 10.1182/blood-2012-10-455055.

    Google Scholar 

  23. Obukhova, P. S. (2012) Specificity of Natural Human Anti-carbohydrate Antibodies in the Norm: Candidate of Science Thesis [in Russian], Shemyakin Institute of Bioorganic Chemistry, RAS, Moscow.

    Google Scholar 

  24. Smorodin, E. P., Kurtenkov, O. A., Sergeyev, B. L., Pazynina, G. V., and Bovin, N. V. (2004) Glycoconj. J., 20, 83–89.

    Article  PubMed  CAS  Google Scholar 

  25. Blixt, O., Lavrova, O. I., Mazurov, D. V., Clo, E., Kracun, S. K., Bovin, N. V., and Filatov, A. V. (2011) Glycobiology, 22, 529–542.

    Article  PubMed  Google Scholar 

  26. Mizutamari, R. K., Wiegandt, H., and Nores, G. A. (1994) J. Neuroimmunol., 50, 215–220.

    Article  PubMed  CAS  Google Scholar 

  27. Grounberg, G., Nilsson, U., Bock, K., and Magnusson, G. (1994) Carbohydr. Res., 257, 35–54.

    Article  Google Scholar 

  28. Bailly, P., and Bouhours, J.-F. (1995) in Blood Cell Biochemistry, Vol. 6 (Cartron, J.-P., and Rouger, P., eds.) Plenum Press, New York, pp. 299–329.

  29. Duk, M., Kuznierz-Alejska, G., Korchagina, E. Y., Bovin, N. V., Bochenek, S., and Lisowska, E. (2005) Glycobiology, 15, 109–118.

    PubMed  CAS  Google Scholar 

  30. Jacob, F., Goldstein, D. R., Huflejt, M., Bovin, N., Pochechueva, T., Spengler, M., Caduff, R., Fink, D., and Heinzelmann-Schwarz, V. (2012) Int. J. Cancer, 130, 138–146; DOI: 10.1002/ijc.26002.

    Article  PubMed  CAS  Google Scholar 

  31. Springer, G. F. (1984) Science, 224, 1198–1206.

    Article  PubMed  CAS  Google Scholar 

  32. Hakomori, S. (1984) Annu. Rev. Immunol., 2, 103–126.

    Article  PubMed  CAS  Google Scholar 

  33. Lloyd, K. O. (1991) Semin. Cancer Biol., 2, 421–431.

    PubMed  CAS  Google Scholar 

  34. Huflejt, M. E., Blixt, O., Vuskovic, M., Xu, H., Shaw, L., Reuben, J. M., Kuerer, H., and Cristofanilli, M. (2005) Br. Cancer Res. Treat., 94(Suppl. 1), S85.

    Google Scholar 

  35. Arun, B., Vuskovic, M., Vasiliu, D., Xu, H., Atchley, D., Chambers, J., Bovin, N. V., Sneige, N., Hortobagyi, G. N., and Huflejt, M. E. (2007) Br. Cancer Res. Treat., 106(Suppl. 1), S180.

    Google Scholar 

  36. Bovin, N. V., and Huflejt, M. E. (2008) Trends Glycosci. Glycotechnol., 20, 245–258.

    Article  CAS  Google Scholar 

  37. Vuskovic, M., Xu, H., Bovin, N., Pass, H., and Huflejt, M. (2011) Int. J. Bioinformatics Res. Appl., 7, 402–426.

    Article  CAS  Google Scholar 

  38. Li, Q., Anver, M. R., Li, Z., Butcher, D. O., and Gildersleeve, J. C. (2010) Int. J. Cancer, 126, 459–468.

    Article  PubMed  CAS  Google Scholar 

  39. Pedersen, J. W., Blixt, O., Bennett, E. P., Tarp, M. A., Dar, I., Mandel, U., Poulsen, S. S., Pedersen, A. E., Rasmussen, S., Jess, P., Clausen, H., and Wandall, H. H. (2011) Int. J. Cancer, 128, 1860–1871; DOI: 10.1002/ijc.25778.

    Article  PubMed  CAS  Google Scholar 

  40. Butvilovskaya, V. I., Popletaeva, S. B., Chechetkin, V. R., Zubtsova, Z. I., Tsybulskaya, M. V., Filippova, M. A., Samokhina, L. O., Vinnitskii, L. I., Ragimov, A. A., Grigoryeva, G. A., Meshalkina, N. Yu., Golysheva, S. V., Shilova, N. V., Bovin, N. V., Zasedatelev, A. S., and Rubina, A. Y. (2013), in preparation.

  41. Smorodin, J. P., Kurtenkov, O. A., Miljukhina, L. M., Sergeyev, B. L., Hint, E. K., Bovin, N. V., Lipping, A. A., and Chuzhmarov, V. J. (1997) Exp. Oncol., 4, 338–342.

    Google Scholar 

  42. Vollmers, H. P., and Brandlein, S. (2007) J. Autoimmun., 29, 295–302.

    Article  PubMed  CAS  Google Scholar 

  43. Newsom-Davis, T. E., Wang, D., Steinman, L., Chen, P. F., Wang, L. X., Simon, A. K., and Screaton, G. R. (2009) Cancer Res., 69, 2018–2025.

    Article  PubMed  CAS  Google Scholar 

  44. Qiu, X., Zhu, X., Zhang, L., Mao, Y., Zhang, J., Hao, P., Li, G., Lu, P., Li, Z., Sun, X., Wu, L., Zheng, J., Deng, Y., Hou, C., Tang, P., Zhang, S., and Zhang, Y. (2003) Cancer Res., 63, 6488–6495.

    PubMed  CAS  Google Scholar 

  45. Dyukova, V. I., Dementieva, E. I., Zubtsov, D. A., Galanina, O. E., Bovin, N. V., and Rubina, A. Y. (2005) Anal. Biochem., 347, 94–105.

    Article  PubMed  CAS  Google Scholar 

  46. Pochechueva, T., Chinarev, A., Spengler, M., Korchagina, E., Heinzelmann-Schwarz, V., Bovin, N., and Rieben, R. (2011) Analyst, 136, 560–569.

    Article  PubMed  CAS  Google Scholar 

  47. Shilova, N. V., Galanina, O. E., Pochechueva, T. V., Chinarev, A. A., Kadykov, V. A., Tuzikov, A. B., and Bovin, N. V. (2005) Glycoconj. J., 22, 43–51.

    Article  PubMed  CAS  Google Scholar 

  48. Pochechueva, T., Jacob, F., Goldstein, D. R., Huflejt, M. E., Chinarev, A., Caduff, R., Fink, D., Hacker, N., Bovin, N. V., and Heinzelmann-Schwarz, V. (2011) Glycoconj. J., 8–9, 507–517.

    Article  Google Scholar 

  49. Shilova, N. V., Navakouski, M. J., Khasbiullina, N., Blixt, O., and Bovin, N. V. (2012) Glycoconj. J., 29, 87–91; DOI: 10.1007/s10719-011-9368-8; PMID: 22258790.

    Article  PubMed  CAS  Google Scholar 

  50. Butschak, G., and Karsten, U. (2002) Tumour Biol., 23, 113–122.

    Article  PubMed  CAS  Google Scholar 

  51. Shilova, N., Huflejt, M. E., Vuskovic, M., Obukhova, P., Navakouski, M., Khasbiullina, N., Pazynina, G., Galanina, O., Bazhenov, A., and Bovin, N. (2013) in Topics Curr. Chem. Sialoglyco Chemistry and Biology (Gerardy-Schahn, R., Dellanoy, P., and von Itzstein, M., eds.) Springer, in press.

  52. Khasbiullina, N. R., Shilova, N. V., Navakouski, M. J., Timofeeva, L. A., Kumar, S., Schwartz-Albiez, R., Sorensen, R. U., Inostroza, J., Bovin, N. V., and Blixt, O. (2012) in 5th Baltic Meet. on Microbial Carbohydrates, Program & Abstracts, Institute of Organic Chemistry, Moscow, p. O26.

    Google Scholar 

  53. Blixt, O., Kumagai-Braesch, M., Tibell, A., Groth, C. G., and Holgersson, J. (2009) Am. J. Transplant., 9, 83–90.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia

    N. V. Bovin

Authors
  1. N. V. Bovin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. V. Bovin.

Additional information

Published in Russian in Biokhimiya, 2013, Vol. 78, No. 7, pp. 1008–1022.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bovin, N.V. Natural antibodies to glycans. Biochemistry Moscow 78, 786–797 (2013). https://doi.org/10.1134/S0006297913070109

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297913070109

Key words

Search

Navigation