Archives of Plastic Surgery

Korean Society of Plastic and Reconstructive Surgeons (대한성형외과학회)
권호 표지
DOI QR코드

DOI QR Code

Immunogenicity of botulinum toxin

  • Wee, Syeo Young (Department of Plastic and Reconstructive Surgery, Soonchunhyang University Gumi Hospital) ;
  • Park, Eun Soo (Department of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital)
  • Received : 2021.04.11
  • Accepted : 2021.11.07
  • Published : 2022.01.15
Download PDF
⟨ Previous Next ⟩

Abstract

Botulinum toxin treatment is the most common non-surgical cosmetic treatment. Although there are many available treatments using botulinum toxin, their effects are temporary and repeated injections are required. These frequent injections can trigger an immunological response. In addition, botulinum toxin acts as an antigen in the body; thus, its effect disappears progressively due to this immunological reaction, which may cause treatment failure. Active botulinum toxin consists of a core neurotoxin and complexing proteins, the exact effects of which remain unclear. However, the complexing proteins are closely related to the immune response and the formation of neutralizing antibodies. Since neutralizing antibodies can lead to treatment failure, their formation should be prevented. Furthermore, various methods of detecting neutralizing antibodies have been used to predict treatment failure.

Keywords

References

  1. Garcia A, Fulton JE Jr. Cosmetic denervation of the muscles of facial expression with botulinum toxin: a dose-response study. Dermatol Surg 1996;22:39-43. https://doi.org/10.1111/j.1524-4725.1996.tb00569.x
  2. Tsui JK. Botulinum toxin as a therapeutic agent. Pharmacol Ther 1996;72:13-24. https://doi.org/10.1016/S0163-7258(96)00091-5
  3. Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol 2010;55:8-14. https://doi.org/10.4103/0019-5154.60343
  4. Sellin LC. The pharmacological mechanism of botulism. Trends Pharmacol Sci 1985;6:80-2. https://doi.org/10.1016/0165-6147(85)90033-1
  5. Munchau A, Bhatia KP. Uses of botulinum toxin injection in medicine today. BMJ 2000;320:161-5. https://doi.org/10.1136/bmj.320.7228.161
  6. Jankovic J. Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatry 2004;75:951-7. https://doi.org/10.1136/jnnp.2003.034702
  7. Guida S, Farnetani F, Nistico SP, et al. New trends in botulinum toxin use in dermatology. Dermatol Pract Concept 2018;8:277-82.
  8. Harii K, Kawashima M. A double-blind, randomized, placebo-controlled, two-dose comparative study of botulinum toxin type A for treating glabellar lines in Japanese subjects. Aesthetic Plast Surg 2008;32:724-30. https://doi.org/10.1007/s00266-008-9199-6
  9. Honeck P, Weiss C, Sterry W, et al. Reproducibility of a fourpoint clinical severity score for glabellar frown lines. Br J Dermatol 2003;149:306-10. https://doi.org/10.1046/j.1365-2133.2003.05436.x
  10. Carruthers JD, Lowe NJ, Menter MA, et al. Double-blind, placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines. Plast Reconstr Surg 2003;112:1089-98.
  11. Won CH, Lee HM, Lee WS, et al. Efficacy and safety of a novel botulinum toxin type A product for the treatment of moderate to severe glabellar lines: a randomized, double-blind, active-controlled multicenter study. Dermatol Surg 2013;39(1 Pt 2):171-8. https://doi.org/10.1111/dsu.12072
  12. Won CH, Kim HK, Kim BJ, et al. Comparative trial of a novel botulinum neurotoxin type A versus onabotulinumtoxinA in the treatment of glabellar lines: a multicenter, randomized, double-blind, active-controlled study. Int J Dermatol 2015;54:227-34. https://doi.org/10.1111/ijd.12627
  13. Scott AB. Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc 1981;79:734-70.
  14. Dressler D. Complete secondary botulinum toxin therapy failure in blepharospasm. J Neurol 2000;247:809-10. https://doi.org/10.1007/s004150070100
  15. Scott AB, Kennedy RA, Stubbs HA. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol 1985;103:347-50. https://doi.org/10.1001/archopht.1985.01050030043017
  16. Frueh BR, Felt DP, Wojno TH, et al. Treatment of blepharospasm with botulinum toxin: a preliminary report. Arch Ophthalmol 1984;102:1464-8. https://doi.org/10.1001/archopht.1984.01040031184014
  17. Benecke R. Clinical relevance of botulinum toxin immunogenicity. BioDrugs 2012;26:e1-9. https://doi.org/10.2165/11599840-000000000-00000
  18. Hsieh PF, Chiu HC, Chen KC, et al. Botulinum toxin A for the treatment of overactive bladder. Toxins (Basel) 2016;8:59. https://doi.org/10.3390/toxins8030059
  19. Dat A, Chin M, Skinner S, et al. Botulinum toxin therapy for chronic anal fissures: where are we at currently? ANZ J Surg 2017;87:E70-3. https://doi.org/10.1111/ans.13329
  20. Camargo CH, Cattai L, Teive HA. Pain relief in cervical dystonia with botulinum toxin treatment. Toxins (Basel) 2015;7:2321-35. https://doi.org/10.3390/toxins7062321
  21. Bhidayasiri R, Truong DD. Evidence for effectiveness of botulinum toxin for hyperhidrosis. J Neural Transm (Vienna) 2008;115:641-5. https://doi.org/10.1007/s00702-007-0812-7
  22. Ferrante FM, Bearn L, Rothrock R, et al. Evidence against trigger point injection technique for the treatment of cervicothoracic myofascial pain with botulinum toxin type A. Anesthesiology 2005;103:377-83. https://doi.org/10.1097/00000542-200508000-00021
  23. Inoue K, Fujinaga Y, Watanabe T, et al. Molecular composition of Clostridium botulinum type A progenitor toxins. Infect Immun 1996;64:1589-94. https://doi.org/10.1128/iai.64.5.1589-1594.1996
  24. Sharma SK, Singh BR. Immunological properties of Hn-33 purified from type A Clostridium botulinum. J Nat Toxins 2000;9:357-62.
  25. Kukreja RV, Singh BR. Comparative role of neurotoxin-associated proteins in the structural stability and endopeptidase activity of botulinum neurotoxin complex types A and E. Biochemistry 2007;46:14316-24. https://doi.org/10.1021/bi701564f
  26. Kwak S, Kang WH, Rhee CH, et al. Comparative pharmacodynamics study of 3 different botulinum toxin type A preparations in mice. Dermatol Surg 2020;46:e132-8. https://doi.org/10.1097/DSS.0000000000002402
  27. Bellows S, Jankovic J. Immunogenicity associated with botulinum toxin treatment. Toxins (Basel) 2019;11:491. https://doi.org/10.3390/toxins11090491
  28. Dong M, Yeh F, Tepp WH, et al. SV2 is the protein receptor for botulinum neurotoxin A. Science 2006;312:592-6. https://doi.org/10.1126/science.1123654
  29. Pirazzini M, Rossetto O, Eleopra R, et al. Botulinum neurotoxins: biology, pharmacology, and toxicology. Pharmacol Rev 2017;69:200-35. https://doi.org/10.1124/pr.116.012658
  30. Dressler D, Bigalke H. Immunological aspects of botulinum toxin therapy. Expert Rev Neurother 2017;17:487-94. https://doi.org/10.1080/14737175.2017.1262258
  31. Stanley EF, Drachman DB. Botulinum toxin blocks quantal but not non-quantal release of ACh at the neuromuscular junction. Brain Res 1983;261:172-5. https://doi.org/10.1016/0006-8993(83)91300-8
  32. Kukreja R, Chang TW, Cai S, et al. Immunological characterization of the subunits of type A botulinum neurotoxin and different components of its associated proteins. Toxicon 2009;53:616-24. https://doi.org/10.1016/j.toxicon.2009.01.017
  33. Naumann M, Boo LM, Ackerman AH, et al. Immunogenicity of botulinum toxins. J Neural Transm (Vienna) 2013;120:275-90. https://doi.org/10.1007/s00702-012-0893-9
  34. Hasegawa K, Watanabe T, Suzuki T, et al. A novel subunit structure of Clostridium botulinum serotype D toxin complex with three extended arms. J Biol Chem 2007;282:24777-83. https://doi.org/10.1074/jbc.M703446200
  35. Ellenhorn MJ, Barceloux DG. Medical toxicology: diagnosis and treatment of human poisoning. New York: Elsevier; 1988. p. 1185-7.
  36. Fujinaga Y. Transport of bacterial toxins into target cells: pathways followed by cholera toxin and botulinum progenitor toxin. J Biochem 2006;140:155-60. https://doi.org/10.1093/jb/mvj161
  37. Park JY, Sunga O, Wanitphakdeedecha R, et al. Neurotoxin impurities: a review of threats to efficacy. Plast Reconstr Surg Glob Open 2020;8:e2627. https://doi.org/10.1097/gox.0000000000002627
  38. Ravenni R, De Grandis D, Mazza A. Conversion ratio between Dysport and Botox in clinical practice: an overview of available evidence. Neurol Sci 2013;34:1043-8. https://doi.org/10.1007/s10072-013-1357-1
  39. Carruthers J, Fournier N, Kerscher M, et al. The convergence of medicine and neurotoxins: a focus on botulinum toxin type A and its application in aesthetic medicine: a global, evidence-based botulinum toxin consensus education initiative. Part II: incorporating botulinum toxin into aesthetic clinical practice. Dermatol Surg 2013;39(3 Pt 2):510-25. https://doi.org/10.1111/dsu.12148
  40. Lorenc ZP, Kenkel JM, Fagien S, et al. Consensus panel's assessment and recommendations on the use of 3 botulinum toxin type A products in facial aesthetics. Aesthet Surg J 2013;33(1 Suppl):35S-40S. https://doi.org/10.1177/1090820X13480479
  41. Krebs KM, Lebeda FJ. Comparison of the structural features of botulinum neurotoxin and NTNH, a non-toxic accessory protein of the progenitor complex. Botulinum J 2008:1:116-34. https://doi.org/10.1504/TBJ.2008.018954
  42. Frevert J. Content of botulinum neurotoxin in Botox®/Vistabel®, Dysport®/Azzalure®, and Xeomin®/Bocouture®. Drugs R D 2010;10:67-73. https://doi.org/10.2165/11584780-000000000-00000
  43. Kerscher M, Roll S, Becker A, et al. Comparison of the spread of three botulinum toxin type A preparations. Arch Dermatol Res 2012;304:155-61. https://doi.org/10.1007/s00403-011-1179-z
  44. Frevert J. Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type A products. Drugs R D 2015;15:1-9. https://doi.org/10.1007/s40268-014-0077-1
  45. Ohishi I, Sugii S, Sakaguchi G. Oral toxicities of Clostridium botulinum toxins in response to molecular size. Infect Immun 1977;16:107-9. https://doi.org/10.1128/iai.16.1.107-109.1977
  46. Chen F, Kuziemko GM, Stevens RC. Biophysical characterization of the stability of the 150-kilodalton botulinum toxin, the nontoxic component, and the 900-kilodalton botulinum toxin complex species. Infect Immun 1998;66:2420-5. https://doi.org/10.1128/iai.66.6.2420-2425.1998
  47. Frevert J, Dressler D. Complexing proteins in botulinum toxin type A drugs: a help or a hindrance? Biologics 2010;4:325-32. https://doi.org/10.2147/BTT.S14902
  48. Johnson EA, Bradshaw M. Clostridium botulinum and its neurotoxins: a metabolic and cellular perspective. Toxicon 2001;39:1703-22. https://doi.org/10.1016/S0041-0101(01)00157-X
  49. Grein S, Mander GJ, Taylor HV. Xeomin® is stable without refrigeration: Complexing proteins are not required for stability of botulinum neurotoxin type A preparations. Toxicon 2008;51 Suppl 1:13. https://doi.org/10.1016/j.toxicon.2008.04.038
  50. de Almeida AT, De Boulle K. Diffusion characteristics of botulinum neurotoxin products and their clinical significance in cosmetic applications. J Cosmet Laser Ther 2007;9 Suppl 1:17-22. https://doi.org/10.1080/17429590701523794
  51. Dodd SL, Rowell BA, Vrabas IS, et al. A comparison of the spread of three formulations of botulinum neurotoxin A as determined by effects on muscle function. Eur J Neurol 1998;5:181-6. https://doi.org/10.1046/j.1468-1331.1998.520181.x
  52. Tang-Liu DD, Aoki KR, Dolly JO, et al. Intramuscular injection of 125I-botulinum neurotoxin-complex versus 125Ibotulinum-free neurotoxin: time course of tissue distribution. Toxicon 2003;42:461-9. https://doi.org/10.1016/S0041-0101(03)00196-X
  53. Frevert J. Xeomin is free from complexing proteins. Toxicon 2009;54:697-701. https://doi.org/10.1016/j.toxicon.2009.03.010
  54. Pingel J, Nielsen MS, Lauridsen T, et al. Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures. Sci Rep 2017;7:14746. https://doi.org/10.1038/s41598-017-14997-3
  55. Seo MS, Kim YI, Kang KK, et al. Comparison study of the response with botulinum toxin muscle injection in the ICR mice from three different sources. Lab Anim Res 2019;35:11. https://doi.org/10.1186/s42826-019-0010-4
  56. Wang L, Sun Y, Yang W, et al. Type A botulinum neurotoxin complex proteins differentially modulate host response of neuronal cells. Toxicon 2014;82:52-60. https://doi.org/10.1016/j.toxicon.2014.02.004
  57. Goschel H, Wohlfarth K, Frevert J, et al. Botulinum A toxin therapy: neutralizing and nonneutralizing antibodies. Therapeutic consequences. Exp Neurol 1997;147:96-102. https://doi.org/10.1006/exnr.1997.6580
  58. Sankhla C, Jankovic J, Duane D. Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections. Mov Disord 1998;13:150-4. https://doi.org/10.1002/mds.870130128
  59. Dressler D, Bigalke H. Botulinum toxin antibody type A titres after cessation of botulinum toxin therapy. Mov Disord 2002;17:170-3. https://doi.org/10.1002/mds.1238
  60. Dressler D. Clinical presentation and management of antibody-induced failure of botulinum toxin therapy. Mov Disord 2004;19 Suppl 8:S92-100. https://doi.org/10.1002/mds.20022
  61. Kromminga A, Schellekens H. Antibodies against erythropoietin and other protein-based therapeutics: an overview. Ann N Y Acad Sci 2005;1050:257-65. https://doi.org/10.1196/annals.1313.027
  62. Albrecht P, Jansen A, Lee JI, et al. High prevalence of neutralizing antibodies after long-term botulinum neurotoxin therapy. Neurology 2019;92:e48-54. https://doi.org/10.1212/wnl.0000000000006688
  63. Naumann M, Carruthers A, Carruthers J, et al. Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX®) across multiple indications. Mov Disord 2010;25:2211-8. https://doi.org/10.1002/mds.23254
  64. Rahman E, Alhitmi HK, Mosahebi A. Immunogenicity to botulinum toxin type A: a systematic review with metaanalysis across therapeutic indications. Aesthet Surg J 2022;42:106-20. https://doi.org/10.1093/asj/sjab058
  65. Wang C, Sun T, Li H, et al. Hypersensitivity caused by cosmetic injection: systematic review and case report. Aesthetic Plast Surg 2021;45:263-72. https://doi.org/10.1007/s00266-020-01684-4
  66. Moon IJ, Chang SE, Kim SD. First case of anaphylaxis after botulinum toxin type A injection. Clin Exp Dermatol 2017;42:760-2. https://doi.org/10.1111/ced.13108
  67. Torres S, Hamilton M, Sanches E, et al. Neutralizing antibodies to botulinum neurotoxin type A in aesthetic medicine: five case reports. Clin Cosmet Investig Dermatol 2013;7:11-7. https://doi.org/10.2147/CCID.S51938
  68. Coleman WP 3rd, Sattler G, Weissenberger P, et al. Safety of incobotulinumtoxinA in the treatment of facial lines: results from a pooled analysis of randomized, prospective, controlled clinical studies. Dermatol Surg 2017;43 Suppl 3:S293-303. https://doi.org/10.1097/DSS.0000000000001409
  69. Atassi MZ. Basic immunological aspects of botulinum toxin therapy. Mov Disord 2004;19 Suppl 8:S68-84. https://doi.org/10.1002/mds.20020
  70. Dressler D, Bigalke H, Benecke R. Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure. J Neurol 2003;250:967-9. https://doi.org/10.1007/s00415-003-1129-6
  71. Dressler D, Zettl U, Benecke R, et al. Can intravenous immunoglobulin improve antibody-mediated botulinum toxin therapy failure? Mov Disord 2000;15:1279-81. https://doi.org/10.1002/1531-8257(200011)15:6<1279::AID-MDS1040>3.0.CO;2-4
  72. Hanna PA, Jankovic J. Mouse bioassay versus Western blot assay for botulinum toxin antibodies: correlation with clinical response. Neurology 1998;50:1624-9. https://doi.org/10.1212/WNL.50.6.1624
  73. Gordon PH, Gooch CL, Greene PE. Extensor digitorum brevis test and resistance to botulinum toxin type A. Muscle Nerve 2002;26:828-31. https://doi.org/10.1002/mus.10231
  74. Dressler D, Bigalke H, Rothwell JC. The sternocleidomastoid test: an in vivo assay to investigate botulinum toxin antibody formation in humans. J Neurol 2000;247:630-2. https://doi.org/10.1007/s004150070132
  75. Voller B, Moraru E, Auff E, et al. Ninhydrin sweat test: a simple method for detecting antibodies neutralizing botulinum toxin type A. Mov Disord 2004;19:943-7. https://doi.org/10.1002/mds.20073