Клещевой энцефалит: иммунологические показатели возможного перехода острой стадии в хроническое течение болезни

Ряд аутоиммунных заболеваний с хроническим течением характеризуются обнаружением в крови больных ДНКаутоантител, в то время как их не содержит кровь здоровых доноров или пациентов с острым течением заболеваний, незначительным нарушением иммунного статуса, без определенной склонности к переходу в хронический процесс. Клещевой энцефалит (КЭ) не рассматривался с этих позиций. Предварительно для данной работы проведен поиск достаточно точных критериев обнаружения ДНК-активности антител иммуноглобулина (Ig) G из сыворотки крови больных КЭ и здоровых доноров. Показано, что относительная активность антител IgG значительно варьирует у пациентов, но большинство образцов (91%) имели определяемый уровень ДНКазной активности. Поликлональные ДНКазные антитела IgG не активировались в присутствии ЭДТА или после диализа с ЭДТА, но могли активироваться некоторыми добавленными ионами металлов с уровнем активности, уменьшающимся в ряду Mn2+ + Ca2+ ≥ Mn2+ + Mg2+ ≥ Mn2+ ≥ Mg2+ + Ca2+ ≥ Co2+ ≥ Mg2+ > Ca2+, в то время как K+ , Na+ , Ni2+, Zn2+ и Cu2+ не стимулировали гидролиз ДНК. Аффинная хроматография на ДНК-целлюлозе разделила ДНКазные антитела IgG на множество субфракций с различным сродством к ДНК и очень разными уровнями относительной активности. Возможные причины каталитического разнообразия поликлональных человеческих аутоантител обсуждаются.

1. Andrievskaya O.A., Buneva V.N., Naumov V.A., Nevinsky G.A. Catalytic heterogeneity of polyclonal RNA-hydrolyzing IgM from sera of patients with lupus erythematosus//Med. Sci. Monit. 2000. № 6. P. 460-470.

2. Andrievskaya O.A., Buneva V.N., Baranovsky A.G. et al. Catalytic diversity of polyclonal RNA-hydrolyzing IgG antibodies from the sera of patients with lupus erythematosus//Immunol. Lett. 2002. № 81. P. 191-198.

3. Andryushkova A.A., Kuznetsova I.A., Buneva V.N. et al. Formation of different abzymes in autoimmune-prone MRL-lpr/lpr mice is associated with changes in colony formation of haematopoietic progenitors//J. Cell. Mol. Med. 2007. № 11. P. 531-551.

4. Anti-RNase Antibodies against pancreatic ribonuclease A hydrolyze RNA and DNA//Int. Immunol. 2008. № 20. P. 1031-1040.

5. Baranova S.V., Buneva V.N., Kharitonova M.A. et al. HIV-1 integrase hydrolyzing antibodies from the sera of HIV-infected patients//Biochimie. 2009. № 9. P. 1081-1086.

6. Baranovsky A.G., Ershova N.A., Buneva V.N. et al. Catalytic heterogeneity of polyclonal DNA-hydrolyzing antibodies from the sera of patients with multiple sclerosis//Immunol. Lett. 2001. № 76. P. 163-167.

7. Baranovsky A.G., Kanyshkova T.G., Mogelnitskii A.S. et al. Polyclonal antibodies from blood and cerebrospinal fluid of patients with multiple sclerosis effectively hydrolyze DNA and RNA//Biochemistry. 1998. № 63. P. 1239-1248.

8. Baranovsky A.G., Matushin V.G., Vlassov A.V. et al. DNA-and RNA-hydrolyzing antibodies from the blood of patients with various forms of viral hepatitis//Biochemistry. 1997. № 62. P. 1358-1366.

9. Bernardi G./Ed. P.D. Boyer. The enzymes. N.Y.: Academic Press, 1971.

10. Berneman A., Cuilbert B., Enschrich S., Avrames S. IgG auto-and polyreactivities of normal human sera//Mol. Immunol. 1993. № 30. P. 1499-1510.

11. Blanco F., Kalsi J., Isenberg D.A. Analysis of antibodies to RNA in patients with systemic lupus erythematosus and other autoimmune rheumatic diseases//Clin. Exp. Immunol. 1991. № 86. P. 66-70.

12. Boekel E.T., Siegert C.E., Vrielink G.J. et al. Analyses of CD27(++) plasma cells in peripheral blood from patients with bacterial infections and patients with serum antinuclear antibodies//J. Clin. Immunol. 2007. № 27. P. 467-476.

13. Campbell V.W., Jackson D.A. The effect of divalent cations on the mode of action of DNase I. The initial reaction products produced from covalently closed circular DNA // J. Biol. Chem. 1980. № 255. P. 3726-3735.

14. Coutinho A., Kazatchkine M.D., Avrameas S. Natural autoantibodies//Curr. Opin. Immunol. 1995. № 7. P. 812-818.

15. Fauci A.S., Braunwald E., Kasper D.L. et al. Harrison's Principles of Internal Medicine: 17th ed. McGraw-Hill Professional, 2008.

16. Fersht A. Enzyme Structure and Mechanism: 2nd ed. N.Y.: W.H. Freeman Co., 1985.

17. Founel S., Muller S. Antinucleosome antibodies and T-cell response in systemic lupus erythematosus//Ann. Med. Interne. 2002. № 153. P. 513-519.

18. Gololobov G.V., Chernova E.A., Schourov D.V. et al. Cleavage of supercoiled plasmid DNA by autoantibody Fab fragment: application of the flow linear dichroism technique//Proc. Natl. Acad. Sci. USA. 1995. № 92. P. 254-257.

19. Gottieb A.A., Shwartz R.H. Antigen-RNA interactions//Cell. Immunol. 1972. № 5. P. 341-362.

20. Hentati B., Sato M.N., Payelle B. et al. Beneficial effect of polyclonal immunoglobulins from malaria-infected BALB/c mice on the lupus-like syndrome of (NZB x NZW)F1 mice//Eur. J. Immunol. 1994. № 24. P. 8-15.

21. Hirokawa K., Takasaki Y., Takeuchi K. et al. Anti-TS1-RNA: characterization of novel antibodies against sequence-specific RNA by random RNA selection in patients with Sjogren's syndrome//J. Rheumatol. 2002. № 29. P. 931-937.

22. Ikeda R., Takasaki Y., Hirokawa K. et al. Clinical significance of antibodies to TS1-RNA in patients with mixed connective tissue disease//J. Rheumatol. 2003. № 30. P. 998-1005.

23. Keinan E. (Ed.). Catalytic antibodies. Germany: Wiley-VCH Verlag GmbH and Co. KgaA, 2005. P. 1-586.

24. Kozyr A.V., Kolesnikov A., Aleksandrova E.S. et al. Novel functional activities of anti-DNA autoantibodies from sera of patients with lymphoproliferative and autoimmune diseases//Appl. Biochem. Biotechnol. 1998. № 75. P. 45-61.

25. Krasnorutskii M.A., Buneva V.N., Nevinsky G.A. Antibodies against DNA hydrolyze RNA and DNA//Biochemistry. 2008. № 73. P. 1547-1560.

26. Krasnorutskii M.A., Buneva V.N., Nevinsky G.A. Immunization of rabbits with DNase I produces polyclonal antibodies with DNase and RNase activities//J. Mol. Recognit. 2008. № 21. P. 233-242.

27. Krasnorutskii M.A., Buneva V.N., Nevinsky G.A. Immunization of rabbits with DNase II leads to formation of polyclonal antibodies with DNase and RNase activities//Int. Immunol. 2009. № 21. P. 349-360.

28. Krasnorutskii M.A., Buneva V.N., Nevinsky G.A., Krasnorutskii M.A. Antibodies against RNA hydrolyze RNA and DNA//J. Mol. Recognit. 2008. № 21. P. 338-347.

29. Kubota T. Lessons from a monoclonal antibody to double-stranded DNA//J. Med. Dent. Sci. 1977. № 44. P. 37-44.

30. Kunze U. Conference report of the 10th meeting of the international scientific working group on tick-borne encephalitis (ISW-TBE): combating tick-borne encephalitis: vaccination rates on the rise//Vaccine. 2008. № 26. P. 6738-6740.

31. Kuznetsova I.A., Orlovskaya I.A., Buneva V.N., Nevinsky G.A. Activation of DNA-hydrolyzing antibodies from the sera of autoimmune-prone MRL-lpr/lpr mice by different metal ions//Biochim. Biophys. Acta. 2007. № 1774. P. 884-896.

32. Lacroix-Desmazes S., Bayry J., Kaveri S.V. et al. High levels of catalytic antibodies correlate with favorable outcome in sepsis//Proc. Natl. Acad. Sci. USA. 2005. № 102. P. 4109-4113.

33. Love J.D., Hewitt R.R. The relationship between human serum and human pancreatic DNase I//J. Biol. Chem. 1979. № 254. P. 12588-12594.

34. Marion T.N., Krishan M.R., Desai D.D. et al. Monoclonal anti-DNA antibodies: structure, specificity, and biology//J. Immunol. Methods. 1997. № 11. P. 3-113.

35. Matsiota-Bernard P., Hentati B., Pie S. et al. Beneficial effect of Salmonella typhimurium infection and of immunoglobulins from S. typhimurium-infected mice on the autoimmune disease of (NZB x NZW) F1 mice // Clin. Exp. Immunol. 1996. № 104. P. 228-235.

36. Matsiota-Bernard P., Mahana W., Avrameas S., Nauciel C. Specific and natural antibody production during Salmonella typhimurium infection in genetically susceptible and resistant mice//Immunology. 1993. № 79. P. 375-380.

37. Mitsuhashi S., Saito R., Kurashige S., Yamashugi N. Ribonucleic acid in the immune response//Moll. Cell. Biochem. 1978. № 20. P. 131-147.

38. Nevinsky G.A., Buneva V.N. Catalytic antibodies in healthy humans and patients with autoimmune and viral diseases//J. Cel. Mol. Med. 2003. № 7. P. 265-276.

39. Nevinsky G.A., Buneva V.N. Human catalytic RNA-and DNA-hydrolyzing antibodies//J. Immunol. Methods. 2002. № 269. P. 235-249.

40. Nevinsky G.A., Buneva V.N. Natural catalytic antibodies -abzymes/Ed. E. Keinan. Catalytic antibodies. VCH-Wiley press, 2005. P. 503-567.

41. Nevinsky G.A., Favorova O.O., Buneva V.N. Catalytic antibodies: new characters in the protein repertoire/Ed. E. Golemis. Protein-protein interactions. A molecular cloning manual. New York: Cold Spring Harbor Lab. Press, Cold Spring Harbor, 2002.

42. Nevinsky G.A., Kanyshkova T.G., Semenov D.V. et al. Secretory immunoglobulin A from healthy human mothers' milk catalyzes nucleic acid hydrolysis//Appl. Biochem. Biotechnol. 2000. № 83. P. 115-129.

43. Nishi Y. Evolution of catalytic antibody repertoire in autoimmune mice//J. Immunol. Methods. 2002. № 269. P. 213-233.

44. Odintsova E.S., Buneva V.N., Nevinsky G.A. Casein-hydrolyzing activity of sIgA antibodies from human milk//J. Mol. Recognit. 2005. № 18. P. 413-421.

45. Odintsova E.S., Kharitonova M.A., Baranovskii A.G. et al. DNA-hydrolyzing IgG antibodies from the blood of patients with acquired immune deficiency syndrome//Mol. Biol. 2006. № 40. P. 857-864.

46. Odintsova E.S., Kharitonova M.A., Baranovskii A.G. et al. Proteolytic activity of IgG antibodies from blood of acquired immunodeficiency syndrome patients//Biochemistry. 2006. № 71. P. 251-261.

47. Paul S. Mechanism and functional role of antibody catalysis//Appl. Biochem. Biotechnol. 1998. № 75. P. 13-23.

48. Polosukhina D.I., Kanyshkova T.G., Doronin B.M. et al. Hydrolysis of myelin basic protein by polyclonal catalytic IgGs from the sera of patients with multiple sclerosis//J. Cell. Mol. Med. 2004. № 8. P. 359-368.

49. Polosukhina D.I., Kanyshkova T.G., Doronin B.M. et al. Metal-dependent hydrolysis of myelin basic protein by IgGs from the sera of patients with multiple sclerosis//Immunol. Lett. 2006. № 103. P. 75-81.

50. Ponamorenko N.A., Durova O.M., Vorobiev I.I. et al. Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen//Proc. Natl. Acad. Sci. USA. 2006. № 103. P. 281-286.

51. Raz E., Ben-Bassat H., Davidi T. et al. Cross-reactions of anti-DNA autoantibodies with cell surface proteins//Eur. J. Immunol. 1993. № 23. P. 383-390.

52. Sato T., Uvhiumi T., Arakawa M., Kominami R. Serological association of lupus autoantibodies to a limited functional domain of 28S ribosomal RNA and to the ribosomal proteins bound to the domain//Clin. Exp. Immunol. 1994. № 98. P. 35-39.

53. Shoenfeld Y., Ben-Yehuda O., Messinger Y. et al. Autoimmune diseases other than lupus share common anti-DNA idiotypes//Immunol. Lett. 1988. № 17. P. 285-291.

54. Shuster A.M., Gololobov G.V., Kvashuk O.A. et al. DNA hydrolyzing autoantibodies//Science. 1992. № 256. P. 665-667.

55. Sinohara H., Matsuura K. Does catalytic activity of Bence-Jones proteins contribute to the pathogenesis of multiple myeloma?//Appl. Biochem. Biotechnol. 2000. № 83. P. 85-94.

56. Steinman L. Multiple sclerosis: a two-stage disease//Nat. Immunol. 2001. V. 2. P. 762-764.

57. Suck D. DNA recognition by DNase I//J. Mol. Recognit. 1994. № 7. P. 65-70.

58. Tanaka H., Sasaki I., Yamashita K. et al. Affinity chromatography of porcine pancreas deoxyribonuclease I on DNA-binding sepharose under non-digestive conditions, using its substrate-binding site//J. Biochem. (Tokyo). 1980. № 88. P. 797-806.

59. Tawfik D.S., Chap R., Green B.S. et al. Unexpectedly high occurrence of catalytic antibodies in MRL/lpr and SJL mice immunized with a transition-state analog: is there a linkage to autoimmunity?//Proc. Natl. Acad. Sci. USA. 2002. № 92. 2145-2149.

60. Ternynck T., Falanga P.B., Unterkircher C. et al. Induction of high levels of IgG autoantibodies in mice infected with Plasmodium chabaudi//Int. Immunol. 1991. № 3. P. 29-37.

61. Unterkircher C., Avrameas S., Ternynck T. Autoantibodies in the sera of Trypanosoma cruzi-infected individuals with or without clinical Chagas disease//J. Clin. Lab. Anal. 1993. № 7. P. 60-69.

62. Wun H.L., Leung D.T., Wong K.C. et al. Molecular mimicry: anti-DNA antibodies may arise inadvertently as a response to antibodies generated to microorganisms//Int. Immunol. 2001. № 13. P. 1099-1107.

63. Yasuda T., Takeshita H., Nakajita H. et al. Rabbit DNase I: purification from urine, immunological and proteochemical characterization, nucleotide sequence, expression in tissues, relationships with other mammalian DNases I and phylogenetic analysis//Biochem. J. 1997. № 325. P. 465-473.