Autoimmune Diseases and Immunoadsorption Therapy

Yıl 2011, Cilt: 39 Sayı: 3, 213 - 229, 01.08.2011

Adil Denizli

Öz

The human immune system is structured to recognize, respond to, and destroy a wide variety of potentially harmful microorganisms. One major component of this defense system depends on its ability to recognize foreign antigens versus healthy cells or tissues. When the immune system begins to destroy vital cells and organs within the body, the resulting reaction can be the basis for certain autoimmune diseases. Immunoadsorption, an extracorporeal technique for the removal of autoantibodies from patient plasma, offers some advantages over plasmapheresis. Immunoadsorption appeared relatively rapid and safe for the extensive removal of pathogenic antibodies and immune-complexes. During the mid 1970’s the first application of therapeutic intervention with immunoadsorbents was reported. In this review, some selected applications on immunoadsorption therapies mainly for removal of anti-dsDNA antibodies from systemic lupus erythematosus SLE and rheumatoid factors from rheumatoid arthritis patients plasmas are briefly discussed.

Anahtar Kelimeler

Autoimmune diseases, immunoadsorption, affinity adsorption, Affinity therapy

Otoimmun Hastalıklar ve İmmunoadsorpsiyon Tedavisi

Öz

İ nsan bağışıklık sistemi, zararlı olabilecek bir çok mikroorganizmayı tanıma, karşılık verme ve yok etmeye yönelik düzenlenmiştir. Bu savunma sisteminin temel bileşeni, sağlıklı hücre ve dokulardan yabancı antijenleri ayırt edebilme özelliğine dayanmaktadır. Bağışıklık sisteminin vücut içerisindeki önemli hücre ve dokuları yok etmeye başlamasıyla oluşan reaksiyon bir otoimmun hastalığa sebep olabilmektedir. Hasta plazmasından otoantibadilerin uzaklaştırılması için uygulanan bir ekstrakorporal teknik olan immunoadsorpsiyon, plazmafereze göre önemli avantajlar sunmaktadır. İmmunoadsorpsiyon, patojenik antibadilerin ve immunkomplekslerin uzun süreli uzaklaştırılmasında daha hızlı ve güvenilirdir. İmmunoadsorpsiyonla ilk tedavi amaçlı müdahele 1970’lerin ortalarında uygulanmıştır. Bu derlemede, sistemik lupus eritematos’lu ve romatoid artrit’li plazmalarından antidsDNA antibadilerin ve romatoid faktörlerinin uzaklaştırılması için uygulanılan immunoadsorpsiyon tedavilerine ait seçilen bazı makaleler kısaca tartışılmıştır

Anahtar Kelimeler

Otoimmun hastalıklar, immunoadsorpsiyon, afinite adsorpsiyonu, afinite tedavisi

Kaynakça

• 1. H.D. Massey, R.A. McPherson, Human leukocyte antigen: the major histocompatibility complex of man, in: Henry’s Clinical Diagnosis and Management by Laboratory Methods, W.B. Saunders, 2006.
• 2. S.G. O’Neill, L. Schrieber, Immunotherapy of systemic lupus erythematosus, Autoimmunity Reviews, 2005.
• 3. D.P. D’Cruz, M.A. Khamastra, G.R.V. Hughes, Systemic lupus erythematosus, Lancet, 369 (2007) 587.
• 4. D.S. Terman, I. Stewart, A. Hofmann, R.Carr, R. Harbeck, Specific removal of DNA antibody with an immunoadsorbent, Experientia, 30 (1974) 1493.
• 5. D.S. Terman, I. Stewart, J. Robinette, R. Carr, R. Harbeck, specific removal of DNA antibodies in vivo with an extracorporeal immuno-adsorbent, Clin. Exp. Immunol., 24 (1976) 231.
• 6. D.S. Terman, G. Buffaloe, C. Mattioli, G. Cook, R. Tilquist, M. Sullivan, J.C. Ayus, Extracorporeal immunoadsorption: initial experience in human systemic lupus erythematosus, Lancet, ii (1979) 824.
• 7. P.K. Ray, Extracorporeal adsorption of pathologic gammaglobulins and immune complexes in various diseases including cancer, Plasma Ther. Transfus. Technol., 4 (1984) 289.
• 8. I.M. Nilsson, S.B. Sundquist, A. Ahlberg, S.E. Bergentz, A procedure for removing high titer antibodies by extracorporeal protein A-sepharose adsorption in hemophilia, Blood, 58 (1981) 38.
• 9. I.M. Nilsson, S.B. Sundquist, R. Ljung, L. Holmberg, C. Friburghaus, G. Björlin, Suppression of secondary antibody response by intraveneous immunoglobulin in a patient with hemophilia B and antibodies, Scand. J. Haematol., 30 (1983) 458.
• 10. H. Hoshimoto, H. Tsuda, Y. Kanai, S. Kobayashi, S. Hirose, H. Shinoura, R. Yokahari, M. Kinoshita, Selective removal of anti-DNA and anticardiolipin antibodies by adsorbent plasmapheresis using dextran sulfate columns in patients with SLE, J. Rheumatol., 18 (1990) 545.
• 11. A. Palmer, T. Cairns, F. Dische, G. Gluck, P. Gjorstrup, V. Parons, K. Welsh, D. Taube, Treatment of rapidly progressive glomerulonephritis by extracorporeal immunoadsorption, Nephrol. Dial. Transplant., 6 (1991) 536.
• 12. C.W. Wiesenhutter, B.L. Irish, J.H. Bertram, Treatment of patients with refractory rheumatoid arthritis with extracorporeal protein A immunoadsorption columns: a pilot trial, J. Rheumatol., 21 (1994) 804.
• 13. A. Deodhar, E. Allen, K. Daoud, I. Wahba, Vasculitis secondary to staphylococcal protein A immunoadsorption treatment in rheumatoid arthritis, Semin. in Arthritis Rheum., 31 (2002) 3.
• 14. B. Mugnier, P. Poullin, P. Lefevre, J. Roudier, Clinical improvement in a patient with severe rheumatoid arthritis and chronic hepatitis B after prosorba column immunoadsorption, Arthritis Rheum., 49 (2003) 722.
• 15. D.E. Furst, D. Felson, M. Gendreau, Patients with severe rheumatoid arthritis responding to treatment respond again on retreatment, Arthritis Rheum., 41 (1998) 316.
• 16. D. Felson, D.E. Furst, M. LaValley, et.al., Results of a randomized double blind trial of the Prosorba column for treatment of severe rheumatoid arthritis, Arthritis Rheum., 41 (1998) 364.
• 17. K. Suzuki, The role of immunoadsorption using dextran-sulfate cellulose columns in the treatment of SLE, Therapeutic Apheresis, 4 (2002) 239.
• 18. M. Suenaga, Y. Matsumura, T. Yamada, Successful treatment with immunoadsorption plasmapheresis therepy for Miller-Fisher syndrome, Jpn. J. Apheresis, 15 (1996) 65.
• 19. A. Palmer, Treatment of SLE by extracorporeal immunoadsorption, Lancet, 2 (1988) 272.
• 20. M. Schneider, T. Berning, M. Waldendorf, J. Glaser, U. Gerlach, Immunoadsorbent plasma perfusion in patients with SLE, J. Rheumatology, 17 (1990) 900.
• 21. K. Sugimoto, K. Yamaji, K.S. Yang, Y. Kanai, H. Tsuda, H. Hashimoto, Immunoadsorption plasmapheresis using a phenylalanine column as an effective treatment for lupus nephritis, Therapeutic Apheresis Dialysis, 10 (2006) 187.
• 22. G.H. Stummvoll, U. Julius, K. Derfler, M. Aringer, Immunoadsorption for systemic lupus erythematosus, Atherosclerosis Suppl., 10 (2009) 110.
• 23. M. Gaubitz, M. Seidel, S. Kummer, H. Schotte, A. Perniok, W. Domschke, M. Schneider, Prospective randomized trial of two different immunoadsorbers in severe SLE, J. Autoimmunity, 11 (1998) 495.
• 24. Y. Nagatomo, A. baba, H. Ito, et.al., Specific immunoadsorption therapy using a tryptophan column in patients with refractory heart failure due to dilated cardiomyopathy, J. Clin. Apheresis, 26 (2011) 1.
• 25. E. Peeva, B. Diamond, “Anti-DNA Antibodies” in: “Systemic Lupus Erythematosus” R.G. Lahita, ed., Academic Press Inc., 2004.
• 26. R. H.Scofield, Autoantibodies as predictors of disease, Lancet, 363 (2004) 1544.
• 27. E.M. Tan, P.H. Schur, R.I. Carr and H.G. Kunkel, J. Clin. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus , Invest., 45 (1966) 1732.
• 28. A.C. Gilliam, D. Lang, J.J. Lospalluto, Antibodies to double-stranded DNA: purification and characterization of binding specificities, J. Immunology, 125 (1980) 874.
• 29. D. Koffler, V. Agenollo, R. Thoburn, H.G. Kunkel, Systemic lupus erythematosus: prototype of immune complex nephritis in man. , J. Exp. Med., 134 (1971) 169.
• 30. S. Izui, P.H. Lambert, P.A. Miescher, Determination of anti-DNA antibodies by a modified 125I-labelled DNAbinding test. Elimination of non-specific binding of DNA to non-immunoglobulin basic proteins by using an anionic detergent, Clin. Exp. Immunol., 26 (1976) 425.
• 31. G.H. Stummvoll, M. Aringer, J.S. Smolen, S. Schmaldienst, E. Jimenez-Boj, W.H. Hörl, W.B. Graninger, K. Derfler, IgG immunoadsorption reduces SLE activity and proteinuria: a long term observational study, Ann. Rheum. Dis., 64 (2005) 1015.
• 32. E.J. Lewis, Plasmapheresis therapy is ineffective in SLE, J. Clin. Apheresis, 7 (1992) 153.
• 33. V.G. Nicolaev, V.V. Sarnatskaya, E.V. Eretskaya, E.A. Snezhkova, N.V. Belitser, Determination of anti-DNA antibodies by a modified 125-labelled DNA-binding test. Elimination of non-specific binding of DNA to non-immunoglobulin basic proteins by using an anionic detergent, Clin. Mat., 11 (1992), 125.
• 34. R.C.A. Ventura, R.D.L. Zollner, C. Legallais, M. Vijayalakshmi, S.M.A. Bueno, In vitro removal of human IgG autoantibodies by affinity filtration using immobilized L-histidine onto PEVA hollow fiber membranes, Biomolecular Eng., 17 (2001) 71.
• 35. B. Zhu, H. Iwata, D. Kong, Y. Yu, K. Kato, Y. Ikada, Preparation of DNA-immobilized immunoadsorbent for treatment of SLE, J. Biomater. Sci. Polym. Ed., 3 (1999) 341.
• 36. Y.H. Yu, B.L. He, The preparation of immunoadsorbents and their adsorption properties for anti-DNA antibodies in SLE serum, React. Functl. Polym., 41 (1999) 191.
• 37. K. Kato, Y. Ikada, Immobilization of DNA onto a polymer support and its potentiality as immunoadsorbent, Biotechnol. Bioeng., 51 (1996) 581.
• 38. A.Y. Hershko, Y. Naparstek, Removal of pathogenic autoantibodies by immunoadsorption, Ann. N.Y. Acad. Sci., 1051 (2005) 635.
• 39. S. Aotsuka, T. Fuahashi, N. Tani, M. Okawa-Takatsuji, M. Kimohita, R. Yokohari, Adsorption of anti-dsDNA antibodies by immobilized polyanioic compounds, Clin. Exp. Immunol., 79 (1990) 215.
• 40. P. Biesenbach, S. Schmaldienst, J.S. Smolen, W.H. Horl, K. Derfler, G.H. Stummvoll, Immuno-adsorption in SLE: three different high affinity columns are adequately effective in removing a u to a n ti b o d i e s and controlling disease activity, Atherosclerosis Suppl., 10 (2009) 114.
• 41. J. Rech, A.J. Hueber, S. Kallert, C. Requadt, J.R. Kalden, H. Schulze-Koops, Immunoadsorption and CD20 antibody treatment in a patient with treatment resistant SLE, Ann. Rheum. Dis., 65 (2006) 552.
• 42. Y. Yan, Y.Y. Ting, S.J. Chang, Q.S. Cheng, Q.W. Lie, S.X. Hua, C.R. Hai, W.J. Zhi, A new DNA immune adsorbent for hemoperfusion in SLE therapy: a clinical trial, Artif. Organs., 12 (1988) 444.
• 43. D. Silvestri, N. Barbani, M.L. Coluccio, C. Pegoraro, P. Giusti, C. Cristallini, G. Ciardelli, Poly(ethyleneco-vinyl alcohol) membraes with specific adsorption properties for potential clinical application, Sep. Sci. Technol., 42 (2007) 2829.
• 44. M. Nachman, Kinetic aspects of membrane-based immunoaffinity chromatography, J. Chromatogr., 597 (1992) 167.
• 45. A. Denizli, Preparation of immuno-affinity membranes for cholesterol removal from human plasma, J. Chromatogr. B., 772 (2002) 357.
• 46. W. Shi, Y. Shen, H. Jiang, C. Song, Y. Ma, J. Mu, B. Yang, D. Ge, Lysine attached anodic aluminum oxide-silica affiity membrane for bilirubin removal, J. Membr. Sci., 349 (2010) 333.
• 47. L. Jia, L. Yang, H. Zou, Y. Zhang, J. Zhao, C. Fan, L. Sha, Protein A tangential flow affinity membrane cartridge for extracorporeal immunoadsorption therapy, Biomed. Chromatogr., 13 (1999) 472.
• 48. O. Pitiot, C. Legallais, L. Darnige, M.A. Vijayalakshmi, A potential set up based on histidine hollow fiber membranes for the extracorporeal removal of human antibodies, J. Membr. Sci., 166 (2000) 221.
• 49. L. Darnige, C. Legallais, J. Arvieux, O. Pitiot, M.A. Vijayalakshmi, Functionalized hollow fiber membrane cartridge for adsorption of anticofactor/ antiphospholipid antibodies: a potential tool for treatment, Artif Organs, 23 (1999) 634.
• 50. L. Uzun, H. Yavuz, B. Osman, H. Çelik, A. Denizli, PHEMA based affinity membranes for in-vitro removal of anti-dsDNA antibodies from SLE plasma, Int. J. Biol. Macromol., 47 (2010) 44.
• 51. J. Müller, G. Wallukat, M. Dandel, H. Bieda, K. Brandes, S. Spiegelsberger, E. Nissen, R. Kunze, R. Hetzer, Immunoglobulin adsorption in patients with idiopathic cardiomyopathy, Circulation, 101 (2000) 385.
• 52. M. Jansen, S. Schmaldienst, S. Banyal, P. Quehenberger, I. Pabinger, K. Derfler, British J. Haematology, 112 (2001) 91.
• 53. P. Gjörstrup, E. Berntorp, L. Larsson, I.M. Nilsson, Vox Sang, Kinetic Aspects of the Removal of IgG and Inhibitors in Hemophiliacs Using Protein A Immunoadsorption, 61 (1991) 244.
• 54. N. Braun, C. Erley, R. Klein, I. kotter, J. Saal, T. Risler, Immunoadsorption onto protein A induces remission in SLE, Nephrol. Dial. Transplant., 15 (2000) 1367.
• 55. D.L. Kong, W. Schuett, J. Dai, S. Kunkel, M. Holtz, R. Yamada, Y. Yu, H. Klinkmann, Development of cellulose-DNA immunosorbent, Artif. Organs, 26 (2002) 200.
• 56. D.L. Kong, W. Schuett, H.F. Boeden, S. Kunkel, M. Holtz, G. Matic, R. Yamada, Y.T. Yu, H. Klinkmann, Development of a immunoadsorbent; coupling DNA on sepharose by an efficient activation method, Artif. Organs, 24 (2000) 845.
• 57. S. Takahashi, N. Wada, K. Harada, Immunoadsorbent apheresis eliminates pathogenic IgG in childhood lupus nephritis, Pediatrics Int., 49 (2007) 817.
• 58. Rheumatoid Arthriotis, Booklet, Fresenius Hemocare, Hamburg, Germany, 2000.
• 59. Excorim Immunoadsorption System, Booklet, Excorim AB, Lund, Sweden, 2001.
• 60. A. Kumar, A. Srivastava, Cell separation using cryogelbased affinity chromatography, Nature Protocol, 5 (2010) 1737.
• 61. S. Hajizadeh, H. Kirsebom, B. Mattiasson, Characterization of macroporous carbon-cryostructured particle gel, an adsorbent for small organic molecules, Soft Mater., 6 (2010) 5562.
• 62. O. Kulygin, M. Silverstein, Porous poly(2-hydroxyethyl methacrylate) hydrogels synthesized within high internal phase emulsions, Soft Mater., 3 (2007) 1525.
• 63. A. Denizli, Extracorporeal affinity therapy, Hacettepe J. Biol. Chem., 39 (2011) 93.
• 64. A. Denizli, E. Pişkin, DNA immobilized polyhydroxyethylmethacrylate microbeads for affinity sorption of human IgG and anti-DNA anti bodies, J. Chromatogr. B, 666 (1995) 215.
• 65. A. Denizli, E. Pişkin, J. Chromatogr. B., Protein A immobilized PHEMA beads for affinity sorption of human IgG, 668 (1995) 13.
• 66. A. Denizli, E.Pişkin, Heparin immobilized PHEMA microbeads for Cholesterol Removal: a preliminary report, J. Chromatogr. B, 670 (1995) 157.
• 67. N. Bereli, M. Andac, G. Baydemir, R. Say, I.Y. Galaev, A. Denizli, Protein recognition via ion-coordinated molecularly imprinted supermacroporous cryogels, J. Chromatogr. A, 1190 (2008) 18.
• 68. D. Türkmen, H. Yavuz, A. Denizli, Synthesis of tentacle type magnetic beads as immobilized metal ch elate affinity support for cytochrome c adsorption, Int. J. Biol. Macromol., 38 (2006) 126.
• 69. E. Özgür, N. Bereli, D. Türkmen, S. Ünal, A. Denizli, PHEMA cryogel for in-vitro removal of anti-dsDNA antibodies from SLE plasma, Mater. Sci. Eng. C, 2011 (in press).
• 70. V.I. Lozinsky, I.Y. Galaev, F.M. Plieva, I.N. Savina, H. Jungvid, B. Mattiasson, Polymeric cryogels as promising materials Trends in Biotechnol., 21 (2003) 445
• 71. A. Kumar, M. Kamihira, I.Y. Galaev, B. Mattiasson, S. Tjima, Type-specific separation of animal cells in auqeous two-phase systems using antibody conjugates with temperature sensitive polymers, Biotechnol. Bioeng., 75 (2001) 570.
• 72. M.B. Daniak, I.Y. Galaev, B. Mattiasson, Affinity cryogel monliths for screening for optimal separation conditions and chromatographic separation of cells, J. Chromatogr. A., 1123 (2006) 122.
• 73. C. Babaç, H. Yavuz, I.Y. Galaev, E. Pişkin, A. Denizli, Binding of antibodies to concanavalin A-modified monolithic cryogel, React. Functl. Polym., 66 (2006) 1263.
• 74. H. Alkan, N. Bereli, Z. Baysal, A. Denizli, Antibody purification with protein A attached super macroporous PHEMA cryogel, Biochem. Eng. J. 45 (2009) 201.
• 75. F. Yılmaz, N. Bereli, H. Yavuz, A. Denizli, Supermacroporous hydrophobic affinity cryogels for protein chromatography, Biochem. Eng. J., 43 (2009) 272.
• 76. S. Asliyuce, N. Bereli, L. Uzun, M.A. Onur, R. Say, A. Denizli, Ion-imprinted supermacroporous cr yogel for in-vitro removal of iron out of human plasma with beta thalassemia, Sep. Purif. Technol., 73 (2010) 243.
• 77. H. Amital, M.H. Harel, R. Ulmansky, M. Harlev, E. Toubi, A. Hersko, Y. Naparstek, Antibodies against the laminin epitoper correlate with SLE disease activity and can be removed by extracorporeal immunoadsorption, Rheumatology, 46 (2007) 1433.
• 78. D. Falkenhagen, M. Brandl, J. Hartmann, KH. Kellner, T. Posnicek, V. Veber, Fluidized bed adsorbent systems for extracorporeal liver support, Therapeuric Aphreresis Dialysis, 10 (2006) 154.
• 79. S. Schmaldienst, M. Mullner, A. Goldmamer, S. Spitzauer, S. Banyai, W.H. Horl, K. Derfler, Intravenous immunoglobulin application following immunoadsorption, Rheumatology, 40 (2001) 513.
• 80. M. Odabaşı, A. Denizli, PHEMA based magnetic DNAaffinity beads for anti-DNA antibody removal from systemic lupus erythematosus patient plasma, J. Chromatogr.B, 760 (2001) 137.
• 81. M. Odabaşı, N. Özkayar, S. Özkara, S. Ünal, A. Denizli, Pathogenic antibody removal using magnetically stabilized fluidized bed, J. Chromatogr. B, 826 (2005) 50.
• 82. A. Denizli, Heparin immobilized poly(2-hydroxyethylmethacrylate) based microspheres, J. Appl. Polym. Sci., 74 (1999) 655.
• 83. S. Özkara, S. Akgöl, Y. Çanak, A. Denizli, A novel magnetic adsorbent for IgG purification in magnetically stabilized fluidized bed, Biotechnol. Prog., 20 (2004) 1169.
• 84. M. Kinoshita, S. Aotka, T. Funahashi, N. Tani, R. Yokohari, Selective removal of anti-dsdNA antibodies by immunoadsorption with dextran sulphate in a patient with SLE, Ann. Rheum. Diseases., 48 (1989) 856.
• 85. B. Avenhaus, W. Avengaus, M. Schneider, W. Domschke, M. Gaubitz, Development of an in vitro miniature model to simulate immunoadsorption in patients with SLE, J. Clin. Apher., 17 (2002) 183.
• 86. D.L. Kong, C.Z. Chen, E.F. Lin, Y.T. Yu, Development of cellulose DNA immunoadsorbent, Artificial Organs, 22 (1998) 644.
• 87. V. Strand, New therapies in development for autoimmune diseases: their rationale for combination treatment, Springer Semin. Immunopathol., 23 (2001) 43.
• 88. M.M. Nielen, et.al., Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors, Arthritis Rheum., 50 (2004) 380.
• 89. A.L. Corper, M.K. Sohi, V.R. Bonapura, M. Steinitz, R. Jefferis, A. Feinstein, D. Beale, M.J. Taussig, B.J. Sutton, Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction, Nat.Struct. Biol., 4 (1997) 374.
• 90. M. Tampoia, V. Brescia, A. Fontana, P. Maggiolini, A. Zucano, N. Pansini, Proteomic: new advances in the diagnosis of rheumatoid arthritis, Clin. Chim. Acta, 357 (2005) 219.
• 91. D. Felson, M. LaValley, A.R. Baldassare, et.al., The prosorba column for treatment of refractory rheumatoid arthritis, Arthritis Rheum., 42 (1999) 2153.
• 92. T. Pincus, R.H. Brooks, L.F. Callahan, Prediction of long-term mortality in patients with rheumatoid arthritis according to simple questionnaire and joint count measures , Ann. Intern. Med., 120 (1994) 26.
• 93. T. Pincus, L.F. Callahan, Taking mortality in rheumatoid arthritis seriously - Predictive markers, socioeconomic status and comorbidity, J. Rheumatol., 13 (1986) 841.
• 94. T. O’Neill, J. Simpson, S.J. Smyth, C. Lovell, A. Calin, orphyria cutanea tarda associated with methotrexate therapy, Br. J. Rheum., 32 (1993) 411.
• 95. P. Poullin, N. Announ, B. Mugnier, S. Guis, J. Roudier, P. Lefevre, Protein A immunoadsorption (prosorba column) in the treatment of rheumatoid arthritis, Joint Bone Spine, 72 (2005) 101.
• 96. American Medical Association Panel. JAMA, 253 (1985) 819.
• 97. T. Burnouf, H. Goubranm, M. Radosevich, Application of bioaffinity technology in therapeutic extracorporeal plasmapheresis and large-scale fractionation of human plasma, J. Chromatogr. B., 715 (1998) 65.
• 98. E. Yılmaz, L. Uzun, A.Y. Rad, U. Kalyoncu, S. Ünal, A. Denizli, Specific adsorption of the a u to a n ti b o d i e s from rheumatoid arthritis patient plasma using histidine-containing affinity beads, J. Biomater. Sci. Polym. Ed., 19 (2008) 875.
• 99. Y.Jimbo, M.Saito, Orientation-controlled immobilization of protein molecules on thin organic films deposited by the plasma technique., J. Mol. Electron., 4 (1988) 111.
• 100.A. Denizli, E. Pişkin, Dye-ligand affinity systems, J. Biochem. Biophys. Methods, 49 (2001) 391.
• 101.H. Alkan, N. Bereli, Z. Baysal, A. Denizli, Selective removal of the autoantibodies from rheumatoid arthritis patient plasma using protein A carrying affinity cryogels, Biochem. Eng. J., 51 (2010) 153.
• 102.M. Takamori, T. Maruta, Immunoadsorption in myasthenia gravis based on specific ligands mimicking the immunogenic sites of the acytylcholine receptor, Ther. Apher., 5 (2001) 340.
• 103.M. Haas, N. Mayr, J. Zeitlhofer, A. Goldammer, K. Dertler, Long-term treatment of myasthenia gravis with immunoadsorption, J. Clin. Apheresis, 17 (2002) 84.
• 104.J. Ptak, Changes of plasma proteins after immunoadsorption using Ig-Adsopak column in patients with myasthenia gravis, Transfusion Apheresis Science, 30 (2004) 125.
• 105.W.B. Benny, D,M.C. Sutton, J. Oger, V. Brill, M.J. McAteer, G. Rock, Clinical evaluation of a staphylococal protein A immunoadsorption system in the treatment of myasthenia gravis patients, Transfusion Science, 39 (1999) 682.
• 106.W. Ronspeck, R. Brinckman, R. Egner, F. Gebauer, et.al., Peptide based adsorbers for therapeutic immunoadsorption, Therapeutic Apheresis Dialysis, 7 (2003) 91.