Biochemistry (Moscow)

, Volume 78, Issue 7, pp 786–797 | Cite as

Natural antibodies to glycans

  • N. V. BovinEmail author


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.

Key words

glycans glycan array microchip natural antibodies 



enzyme-linked immunosorbent assay




natural antibodies


printed glycan array


suspension array


sialic acid residue




tumor-associated carbohydrate antigen


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  1. 1.
    George, J., and Shoenfeld, Y. (1996) in Autoantibodies (Peter, J. B., and Shoenfeld, Y., eds.) Elsevier, pp. 534–539.Google Scholar
  2. 2.
    Kaveri, S. V., Silverman, G. J., and Bayry, J. (2012) J. Immunol., 188, 939–945.PubMedCrossRefGoogle Scholar
  3. 3.
    Avrameas, S. (1991) Immunol. Today, 12, 154–159.PubMedGoogle Scholar
  4. 4.
    Galanina, O. E., Mecklenburg, M., Nifantiev, N. E., Pazynina, G. V., and Bovin, N. V. (2003) Lab. Chip, 3, 260–265.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 7.
    Alvarez, R. A., and Blixt, O. (2006) Methods Enzymol., 415, 292–310.PubMedCrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 9.
    The Functional Glycomics Gateway,
  10. 10.
    Park, S., Gildersleeve, J. C., Blixt, O., and Shin, I. (2013) Chem. Soc. Rev., DOI: 10.1039/C2CS35401B.Google Scholar
  11. 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. 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.CrossRefGoogle Scholar
  13. 13.
    Obukhova, P., Korchagina, E., Henry, S., and Bovin, N. (2011) Transfusion, 52, 860–869; PMID: 21981750.PubMedCrossRefGoogle Scholar
  14. 14.
    Obukhova, P., Rieben, R., and Bovin, N. (2007) Xenotransplantation, 14, 627–635.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    Frete, D., Srivastava, V., Hindsgaul, O., and Baenziger, J. U. (1991) Cell, 67, 1103–1110.CrossRefGoogle Scholar
  19. 19.
    Grader-Beck, T., Boin, F., von Gunten, S., Smith, D., Rosen, A., and Bochner, B. S. (2011) Ann. Rheum. Dis., 70, 2218–2224.PubMedCrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 21.
    Ishihara, K., Kurihara, M., Goso, Y., Urata, T., Ota, H., Katsuyama, T., and Hotta, K. (1996) Biochem. J., 318, 409–416.PubMedGoogle Scholar
  22. 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. 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. 24.
    Smorodin, E. P., Kurtenkov, O. A., Sergeyev, B. L., Pazynina, G. V., and Bovin, N. V. (2004) Glycoconj. J., 20, 83–89.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 26.
    Mizutamari, R. K., Wiegandt, H., and Nores, G. A. (1994) J. Neuroimmunol., 50, 215–220.PubMedCrossRefGoogle Scholar
  27. 27.
    Grounberg, G., Nilsson, U., Bock, K., and Magnusson, G. (1994) Carbohydr. Res., 257, 35–54.CrossRefGoogle Scholar
  28. 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.Google Scholar
  29. 29.
    Duk, M., Kuznierz-Alejska, G., Korchagina, E. Y., Bovin, N. V., Bochenek, S., and Lisowska, E. (2005) Glycobiology, 15, 109–118.PubMedGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 31.
    Springer, G. F. (1984) Science, 224, 1198–1206.PubMedCrossRefGoogle Scholar
  32. 32.
    Hakomori, S. (1984) Annu. Rev. Immunol., 2, 103–126.PubMedCrossRefGoogle Scholar
  33. 33.
    Lloyd, K. O. (1991) Semin. Cancer Biol., 2, 421–431.PubMedGoogle Scholar
  34. 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. 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. 36.
    Bovin, N. V., and Huflejt, M. E. (2008) Trends Glycosci. Glycotechnol., 20, 245–258.CrossRefGoogle Scholar
  37. 37.
    Vuskovic, M., Xu, H., Bovin, N., Pass, H., and Huflejt, M. (2011) Int. J. Bioinformatics Res. Appl., 7, 402–426.CrossRefGoogle Scholar
  38. 38.
    Li, Q., Anver, M. R., Li, Z., Butcher, D. O., and Gildersleeve, J. C. (2010) Int. J. Cancer, 126, 459–468.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.Google Scholar
  41. 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. 42.
    Vollmers, H. P., and Brandlein, S. (2007) J. Autoimmun., 29, 295–302.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 46.
    Pochechueva, T., Chinarev, A., Spengler, M., Korchagina, E., Heinzelmann-Schwarz, V., Bovin, N., and Rieben, R. (2011) Analyst, 136, 560–569.PubMedCrossRefGoogle Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. 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.CrossRefGoogle Scholar
  49. 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.PubMedCrossRefGoogle Scholar
  50. 50.
    Butschak, G., and Karsten, U. (2002) Tumour Biol., 23, 113–122.PubMedCrossRefGoogle Scholar
  51. 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.Google Scholar
  52. 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. 53.
    Blixt, O., Kumagai-Braesch, M., Tibell, A., Groth, C. G., and Holgersson, J. (2009) Am. J. Transplant., 9, 83–90.CrossRefGoogle Scholar

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© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  1. 1.Shemyakin-Ovchinnikov Institute of Bioorganic ChemistryRussian Academy of SciencesMoscowRussia

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