ВНУТРИВЕННЫЕ ИММУНОГЛОБУЛИНЫ: МЕХАНИЗМЫ ТЕРАПЕВТИЧЕСКИХ ЭФФЕКТОВ
Аннотация
Внутривенные иммуноглобулины (ВВИГ) представляют собой наиболее широко исполь-
зуемые в настоящее время, иммунобиологические лекарства, получаемые из донорской крови. Они содержат антитела, в подавляющем большинстве класса IgG, полученные из пулов плазмы от 3 000 до 15000 доноров (не менее от 1000 доноров, согласно международным требованиям и руководствам) и уже более 40 лет используются при терапии различных заболеваний. Первое время их применение носило сугубо иммунозаместительный характер при первичных иммуннодефицитных состояниях, но в последние годы клинические и экспериментальные данные, показывают эффективность ВВИГ при системных и аутоиммунных заболеваниях, при иммунологическом бесплодии и невынашивании беременности, в транслантологии, гематологии и других областях медицины. Их эффективность связывают с иммуномодулирующими эффектами. Растет количество публикаций посвященной этой теме, понимание механизмов терапевтических эффектов ВВИГ, которые базируются на последних фундаментальных и клинических научных открытиях в этой области. В тоже время много остается не ясным, противоречивым, а некоторые данные носят и вовсе взаимоисключающий характер. Все это обуславливает интерес к данной группе лекарственных средств. Цель данной статьи – обобщить основные известные механизмы лечебных эффектов, результаты последних исследований в данной области, и возможные перспективные направления использования ВВИГ в будущем.
Об авторах
В. А. Лазанович
ГБОУ ВПО «Тихоокеанский государственный медицинский университет» Минздрава России,
г. Владивосток
Россия
Россия
к.м.н., ассистент кафедры клинической лабораторной диагностики, общей и клинической
иммунологии ГБОУ ВПО «Тихоокеанский государственный медицинский университет» Минздрава России
Е. В. Просекова
ГБОУ ВПО «Тихоокеанский государственный медицинский университет» Минздрава России,
г. Владивосток
Россия
Россия
д.м.н., профессор, заведующая кафедрой клинической лабораторной диагностики, общей
и клинической иммунологии ГБОУ ВПО «Тихоокеанский государственный медицинский университет»
Минздрава России
Список литературы
1. Aktas O., Waiczies S., Grieger U., Wendling U., Zschenderlein R., Zipp F. Polyspecific immunoglobulins (IVIg) suppress proliferation of human (auto) antigen-specific T cells without inducing apoptosis. J. Neuroimmunol., 2001, Vol. 114, no. 1, pp. 160-167.
2. Anthony R.M., Nimmerjahn F., Ashline D.J., Reinhold V.N., Paulson J.C., Ravetch J.V. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science, 2008, Vol. 320, no. 5874, pp. 373-376.
3. Aubin Е., Proulx D.P., Tr panier P., Lemieux R., Bazin R. Prevention of T cell activation by interference of internalized intravenous immunoglobulin (IVIg) with MHC II-dependent native antigen presentation. Clin. Immunol., 2011, Vol. 141, no. 3, pp. 273-283.
4. Aukrust P., Fr land S.S., Liabakk N.B. Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist afterintravenous immunoglobulin administration in vivo. Blood, 1994, Vol. 84, no. 7, pp. 2136-2143.
5. Baker K., Qiao S.W., Kuo T.T., Aveson V.G., Platzer B., Andersen J.T., Sandlie I., Chen Z., de Haar C., Lencer W.I., Fiebiger E., Blumberg R.S. Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc. Natl. Acad. Sci. USA, 2011, Vol. 108, pp. 9927-9932.
6. Baker K., Rath T., Lencer W.I. Cross-presentation of IgG-containing immune complexes. Cell Mol. Life. Sci., 2013, Vol. 70, no. 8, pp. 1319-1334.
7. Basta M., Fries L.F., Frank M.M. High-dose intravenous immunoglobulin inhibits in vitro uptake of C4 fragments onto sensitized erythrocytes. Blood, 1991, Vol. 77, no. 2, pp. 376-380.
8. Bayry J., Lacroix-Desmazes S., Delignat S. Intravenous immunoglobulin abrogates dendritic cell differentiation induced by interferon-alpha present in serum from patients with systemic lupus erythematosus. Arthritis Rheum., 2003, Vol. 48, no. 12, pp. 3497-3502.
9. Bayry J., Lacroix-Desmazes S., Carbonneil C. Inhibition of maturation and function of dendritic cells by intravenous immunoglobulin. Blood, 2003, Vol. 101, no. 2, pp. 758-765.
10. Ben Mkaddem S, Rossato E, Heming N. Anti-inflammatory role of the IgA Fc receptor (CD89): from autoimmunity to therapeutic perspectives. Аutoimmun. Rev., 2013, Vol. 12, no. 6, pp. 666-669.
11. Berger M. Short analytical review: subcutaneous immunoglobulin replacement in primary immunodeficiencies. Clin. Immunol. 2004, Vol. 112, no. 1, pp. 1-7.
12. Bhol K.C., Desai A., Kumari S. Pemphigus vulgaris: the role of IL-1 and IL-1 receptor antagonist in pathogenesis and effects ofintravenous immunoglobulin on their production. Clin. Immunol., 2001, Vol. 100, no. 2, pp. 172-180.
13. Blank M, Anafi L., Zandman-Goddard G. The efficacy of specific IVIG anti-idiotypic antibodies in antiphospholipid syndrome (APS): trophoblast invasiveness and APS animal model. J. Int. Immunol., 2007, Vol. 19, no. 7, pp. 857-865.
14. Blasczyk R., Westhoff U., Grosse-Wilde H. Soluble CD4, CD8, and HLA molecules in commercial immunoglobulin preparations. Lancet, 1993, Vol. 341, pp. 789-790.
15. Bruley-Rosset M., Mouthon L., Chanseaud Y., Dhainaut F., Lirochon J., Bourel D. Polyreactive autoantibodies purified from human intravenous immunoglobulins prevent the development of experimental autoimmune diseases. Lab. Invest., 2003, Vol. 83, no. 7, pp. 1013-1023.
16. Вruton O. Agammaglobulinemia. Pediatrics, 1952, Vol. 9, pp. 722-728.
17. Blank M., Anafi L., Zandman-Goddard G., Krause I., Goldman S., Shalev E., Cervera R., Font J., Fridkin M., Thiesen H.J., Shoenfeld Y. The efficacy of specific IVIG anti-idiotypic antibodies in antiphospholipid syndrome (APS): trophoblast invasiveness and APS animal model. J. Int. Immunol., 2007, Vol. 19, no. 7, pp. 857-865.
18. B hmig G.A., Wahrmann M., Bartel G. Transplantation of the broadly sensitized patient: what are the options? Curr. Opin. Organ Transplant., 2011, Vol. 16, no. 6, pp.588-593.
19. Cousens L.P., Najafian N., Mingozzi F., Elyaman W., Mazer B., Moise L., Messitt T.J., Su Y., Sayegh M., High K., Khoury S.J., Scott D.W., De Groot A.S. In vitro and in vivo studies of IgG-derived Treg epitopes (Tregitopes): a promising new tool for tolerance induction and treatment of autoimmunity. J. Clin. Immunol. 2013, Vol. 33, no. 1, pp. 43-49.
20. Cousens L.P., Tassone R., Mazer B.D. Tregitope update: mechanism of action parallels IVIg. Autoimmun. Rev. 2013, Vol. 12, no. 3, pp. 436-443.
21. Cousens L.P., Su Y., McClaine E., Li X., Terry F., Smith R., Lee J, Martin W., Scott D.W., De Groot A.S. Application of IgG – derived natural treg epitopes (IgG Tregitopes) to antigen-specific tolerance induction in a murine model of type 1 diabetes. J. Diabetes Res., 2013, Vol. 621693, pp. 1-17.
22. Daёron M. Negative regulation of mast cell activation by receptors for IgG. Int. Arch Allergy Immunol., 1997, Vol. 113, no. 3, pp. 138-141.
23. De Groot A.S., Moise L., McMurry J.A. Wambre E., Van Overtvelt L., Moingeon P., Scott D.W., Martin W. Activation of natural regulatory T cells by IgG Fc-derived peptide “Tregitopes”. Blood, 2008, Vol. 112, no. 8, pp. 3303-3311.
24. Denys C., Toungouz M., Dupont E. Increased in vitro immunosuppressive action of anti-CMV and anti-HBs intravenous immunoglobulins due to higher amounts of interferon-gamma specific neutralizing antibodie. Vox Sang., 1997, Vol. 72, no. 4, pp. 247-250.
25. Edberg J.C., Redecha P.B., Salmon J.E. Human FcγRIII (CD16). Isoforms with distinct allelic expression, extracellular domains, and membrane linkages on polymorphonuclear and natural killer cell. J. Immunol., 1989, Vol. 143, no. 5, pp. 1642-1649.
26. Ericson S.G., Coleman K.D., Wardwell K., Baker S., Fanger M.W., Guyre P.M., Ely P. Monoclonal antibody 197 (anti-FcγRI) infusion in a patient with immune thrombocytopenia purpura (ITP) results in downmodulation of Fc gamma RI on circulating monocytes. Br. J. Haematol., 1996, Vol. 92, no. 3, pp. 718-724.
27. Fehr J., Hofmann V., Kappeler. Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gamma globulin. Engl. J. Med. 1982, Vol. 306, no. 21, pp. 1254-1258.
28. Fridman W.H. Fc receptors and immunoglobulin binding factors. FASEB J., 1991, Vol. 5, no. 12, pp. 2684-2690.
29. Fuchs S., Feferman T., Zhu K.Y. Suppression of experimental autoimmune myasthenia gravis by intravenous immunoglobulin and isolation of a disease-specific IgG fraction. J. Ann. N. Y. Acad. Sci., 2007, Vol. 1110, pp. 550-558.
30. Ghetie V., Ward E.S. Multiple roles for the major histocompatibility complex class I-related receptor FcRn. Annu. Rev. Immunol., 2000, Vol. 18, pp. 739-766.
31. Goebl N.A., Babbey C.M., Datta-Mannan A., Witcher D.R., Wroblewski V.J., Dunn K.W. Neonatal Fc receptor mediates internalization of Fc in transfected human endothelial cells. Mol. Biol. Cell., 2008, Vol. 19, no. 12, pp. 5490-5505.
32. Gondolesi G., Blondeau B., Maurette R., Hoppenhauer L., Rodriguez-Laiz G., Schiano T., Boros P., Bromberg J., Akalin E., Sauter B. Pretransplant immunomodulation of highly sensitized small bowel transplant candidates with intravenous immunоglobulin. Transplantation, 2006, Vol. 81, no. 12, pp. 1743-1746.
33. Greenberg M., Frant S., Rutstein D. «Gammaglobulin» and «placental globulin»; comparison of their effectiveness in prevention and modification of measles. JAMA, 1944, Vol. 126, no. 15, pp. 944-947.
34. Huang J.L., Lee W.Y., Chen L.C. Changes of serum levels of interleukin-2, intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1 and Th1 and Th2 cell in severe atopic dermatitis after intravenous immunoglobulin therapy. Ann. Allergy Asthma Immunol., 2000, Vol. 84, no. 3, pp. 345-352.
35. Imbach P., Barandun S., d’Apuzzo V. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet, 1981, pp. 1228-1231.
36. Jerzak M., Rechberger T., G rski A. Intravenous immunoglobulin therapy influences T cell adhesion to extracellular matrix in women with a history of recurrent spontaneous abortions. Am. J. Reprod Immunol., 2000, Vol. 44, no. 6, pp. 3336-3341.
37. Jin M.K., Cho J.H., Kwon O., Hong K.D., Choi J.Y., Yoon S.H., Park S.H., Kim Y.L., Kim C.D. Successful kidney transplantation after desensitization using plasmapheresis, low-dose intravenous immunoglobulin, and rituximab in highly sensitized patients: a single-center experience. Transplant Proc., 2012, Vol. 44, no. 1, pp. 200-203.
38. Jolles S., Sewell W. A., Misbah S.A. Clinical uses of intravenous immunoglobulin. Clin. Exp. Immunol. 2005, Vol. 142, no. 1, pp. 1-11.
39. Jordan S.C., Vo A.A., Peng A. Intravenous gammaglobulin (IVIG): a novel approach to improve transplant rates and outcomes in highly HLA-sensitized patients. Аm. J. Transplant., 2006, Vol. 6, no. 3, pp. 459-466.
40. Jordan S.C., Pescovitz M.D. Presensitization: the problem and its management. Clin. J. Am. Soc. Nephrol., 2006, Vol. 1, no. 3, pp. 421-432.
41. Jordan S.C., Toyoda M., Vo A.A. Regulation of immunity and inflammation by intravenous immunoglobulin: relevance to solid organ transplantation. Expert Rev. Clin. Immunol., 2011, Vol. 7, no. 3, pp. 341-348.
42. Kaneko Y., Nimmerjahn F., Ravetch J.V. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science, 2006, Vol. 313, no. 5787, pp. 670-673.
43. Katz U., Shoenfeld Y., Zandman-Goddard G. Update on intravenous immunoglobulins (IVIg) mechanisms of action and off-label use in autoimmune diseases. Curr. Pharm. Des., 2011, Vol. 17, no. 29, pp. 3166-3175.
44. Kotlan B., Stroncek D.F., Marincola F.M. Intravenous immunoglobulin-based immunotherapy: an arsenal of possibilities for patients and science. Immunotherapy, 2009, Vol. 1, no. 6, pp. 995-1015.
45. Lamari F., Anastassiou E.D., Tsegenidis T., Dimitracopoulos G., Karamanos N.K. An enzyme immunoassay to determine the levels of specific antibodies toward bacterial surface antigens in human immunoglobulin preparations and blood serum. J. Pharm. Biomed. Anal., 1999, Vol. 20, no. 6, pp. 913-920.
46. Lutz H.U., Stammler P., Jelezarova E., Nater M. High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn-IgG complexes. Blood, 1996, Vol. 88, no. 1, pp. 184-193.
47. Maddur M.S., Othy S., Hegde P., Vani J., Lacroix-Desmazes S., Bayry J., Kaveri S.V. Immunomodulation by intravenous immunoglobulin: role of regulatory T cells. J. Clin Immunol., 2010, Vol. 30, no. 1, pp. 4-8.
48. Marchalonis J.J., Kaymaz H., Dedeoglu F. Immune modulatory effects of immunoglobulins on cellmediated immune responses in vitro. Scand J. Immunol., 1993, Vol. 38, pp. 477-484.
49. Mollnes T.E., H g sen K., Hoaas B.F. Inhibition of complement-mediated red cell lysis by immunoglobulins is dependent on the IgG isotype and its C1 binding properties. Scand J. Immunol., 1995, Vol. 41, no. 5, pp. 449-456.
50. Nimmerjahn F., Ravetch J.V. Fc-receptors as regulators of immunity. Advances Immunology, 2007, Vol. 96, pp. 179-204.
51. Ordman C.W., Jennings J.R., Janeway C.A. Chemical, Clinical and Immunological studies on the products of human plasma fractionation. XII. The Use of Concentrated Normal Human Serum Gamma Globulin (Human Immune Serum Globulin) in the Prevention and Attenuation of Measles. J. Clin Invest. 1944, Vol. 23, no. 4, pp. 541-549.
52. Paquin Proulx D., Aubin E., Lemieux R., Bazin R. Inhibition of B cell-mediated antigen presentation by intravenous immunoglobulins (IVIg). Clin. Immunol., 2010, Vol. 135, no. 3, pp. 422-429.
53. Pasquier B., Launay P., Kanamaru Y. Identification of Fc alphaRI as an inhibitory receptor that controls inflammation: dual role of FcRγ ITAM. Immunity, 2005, Vol. 22, no. 1, pp. 31-42.
54. Rath T., Kuo T.T., Baker K., Qiao S.W., Kobayashi K., Yoshida M., Roopenian D., Fiebiger E., Lencer W.I., Blumberg R.S. The immunologic functions of the neonatal Fc receptor for IgG. J. Clin. Immunol., 2013, Vol. 33, no. 1, pp. 9-17.
55. Ravetch J.V., Kinet J.P. Fc receptors. Annu Rev. Immunol., 1991, no. 9, pp. 457-492.
56. Roopenian D.C., Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol., 2007, Vol. 7, no. 9, pp. 715-725.
57. Rossi F., Kazatchkine M.D. Antiidiotypes against autoantibodies in pooled normal human polyspecific Ig. J. Immunol., 1989, Vol. 143, no. 12, pp. 4104-4109.
58. Rossi F., Jayne D.R., Lockwood C.M. Anti-idiotypes against anti-neutrophil cytoplasmic antigen autoantibodies in normal human polyspecific IgG for therapeutic use and in the remission sera of patients with systemic vasculitis. Clin. Exp. Immunol., 1991, Vol. 83, no. 2, pp. 298-303.
59. Semple J.W., Kim M., Lazarus A.H., Freedman J. Gamma-globulins prepared from sera of multiparous women bind anti-HLA antibodies and inhibit an established in vivo human alloimmune response. Вlood, 2002, Vol. 100, no. 3, pp. 1055-1059.
60. Sewell W.A., Jolles S. Immunomodulatory action of intravenous immunoglobulin. Immunology, 2002, Vol. 107, no. 4, pp. 387-393.
61. Silverman G.J., Vas J., Gr nwall C. Protective autoantibodies in the rheumatic diseases: lessons for therapy. Nat. Rev. Rheumatol., 2013, Vol. 9, no. 5, pp. 291-300.
62. Smith K.G., Clatworthy M.R. FcγRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nature Reviews Immunology, 2010, Vol. 674, no. 10, pp. 328-343.
63. Stokes J., Maris E.P., Gellis S.S. 1944 Chemical, Clinical, and Immunological studies on the products of human fractionation. XI. The use of concentrated normal human serum gamma globulin (Human Immune Serum Globulin) in the prophylaxis and treatment of measles. JAMA, 1944, Vol. 23, no. 4, pp. 531-540.
64. Stokes., Neefe Jr. The prevention and attenuation of infectious hepatitis by gamma globulin. Preliminary note. JAMA, 1945, Vol. 127, no. 3, pp. 144-145.
65. Takei S., Arora Y.K., Walker S. M. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens. J. Clin. Invest., 1993, Vol. 91, no. 2, pp. 602-607.
66. Tanimine N., Ide K., Yamashita M., Tanaka Y., Igarashi Y., Banshodani M., Tazawa H., Basnet N.B., Doskali M., Onoe T., Tashiro H., Ohdan H. Kinetics of cellular and humoral immunity in a successful case of positive crossmatch kidney transplantation: a case report. Transplant. Proc., 2011, Vol. 43, no. 6, pp. 2411-2414.
67. Terness P., Opelz G. Natural anti-immunoglobulin autoantibodies: Irrelevant by-products or immunoregulatory molecules? Int. Arch. Allergy Immunol., 1998, Vol. 115, no. 4, pp. 270-277.
68. Tha-In T., Metselaar H.J., Bushell A.R., Kwekkeboom J., Wood K. J. Intravenous immunoglobulins promote skin allograft acceptance by triggering functional activation of CD4+FoxP3+ T cells. Transplantation, 2010, Vol. 89, no. 12, pp. 1446-1455.
69. Trepanier P., Aubin E., Bazin R. IVIg-mediated inhibition of antigen presentation: predominant role of naturally occurring cationic Ig. Clin. Immunol., 2012, Vol. 142, no. 3, pp. 383-389.
70. Vassilev T.L., Kazatchkine M.D., Duong Van Huyen J.P. Inhibition of cell adhesion by antibodies to Arg-Gly-Asp (RGD) in normal immunoglobulin for therapeutic use (intravenous immunoglobulin, IVIg). Blood, 1999, Vol. 93, no. 11, pp. 3624-3631.
71. Viard I., Wehrli P., Bullani R., Schneider P., Holler N., Salomon D., Hunziker T., Saurat J.H., Tschopp J., French L.E. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenousimmunoglobulin. Science, 1998, Vol. 282, pp. 490-493.
72. Vo A.A., Lukovsky M., Toyoda M. Wang J., Reinsmoen N.L., Lai C.H., Peng A., Villicana R., Jordan S.C. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N. Engl. J. Med., 2008, Vol. 359, no. 3, pp. 242-251.
73. Wada J., Shintani N., Kikutani K., Nakae T., Yamauchi T., Takechi K. Intravenous immunoglobulin prevents experimental autoimmune myositis in SJL mice by reducing anti-myosin antibody and by blocking complement deposition. Clin. Exp. Immunol. 2001, Vol. 124, no. 2, pp. 282-289.
74. Young J.D., Ko S.S., Cohn Z.A. The increase in intracellular free calcium associated with IgG gamma 2β/γ 1 Fc receptor – ligand interactions: role in phagocytosis. Proc. Natl. Acad. Sci. USA, 1984, Vol. 81, no. 17, pp. 5430-5434.
Для цитирования:
Лазанович В.А., Просекова Е.В. ВНУТРИВЕННЫЕ ИММУНОГЛОБУЛИНЫ: МЕХАНИЗМЫ ТЕРАПЕВТИЧЕСКИХ ЭФФЕКТОВ. Медицинская иммунология. 2014;16(4):311-322. https://doi.org/10.15789/1563-0625-2014-4-311-322
For citation:
Lazanovich V.A., Prosekova E.V. INTRAVENOUS IMMUNOGLOBULINS: MECHANISMS OF THERAPEUTIC EFFECTS. Medical Immunology (Russia). 2014;16(4):311-322. (In Russ.) https://doi.org/10.15789/1563-0625-2014-4-311-322
Просмотров: 1165
Послать статью по эл. почте 