Immunogenicity of Botulinum Toxin A: Insights.
Journal
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]
ISSN: 1524-4725
Titre abrégé: Dermatol Surg
Pays: United States
ID NLM: 9504371
Informations de publication
Date de publication:
01 Sep 2024
01 Sep 2024
Historique:
medline:
29
8
2024
pubmed:
29
8
2024
entrez:
28
8
2024
Statut:
ppublish
Résumé
Botulinum toxin A (BoNT-A) is widely used in treating dystonia and spasticity to managing chronic migraine and cosmetic applications. However, its immunogenic potential presents challenges, such as the development of neutralizing antibodies that lead to diminished therapeutic efficacy over time, known as secondary nonresponse. This review aims to bridge the knowledge gap regarding the immunogenic mechanisms of BoNT-A and to explore effective management strategies to mitigate these immune responses. The authors conducted a systematic search in databases including PubMed, Embase, and Web of Science, using keywords related to BoNT-A's immunogenicity. The selection process refined 157 initial articles down to 23 relevant studies, which underwent analysis to investigate the underlying mechanisms of immunogenicity and the factors influencing it. The analysis revealed that both the neurotoxin component and the neurotoxin-associated proteins could elicit an immune response. However, only antibodies against the core toxin influence therapeutic outcomes. Various patient-specific factors such as genetic predispositions and prior immune experiences, along with treatment-related factors such as dosage and frequency, play crucial roles in shaping these responses. Understanding the specific immunogenic triggers and responses to BoNT-A is critical for optimizing treatment protocols and improving patient outcomes.
Sections du résumé
BACKGROUND
BACKGROUND
Botulinum toxin A (BoNT-A) is widely used in treating dystonia and spasticity to managing chronic migraine and cosmetic applications. However, its immunogenic potential presents challenges, such as the development of neutralizing antibodies that lead to diminished therapeutic efficacy over time, known as secondary nonresponse.
OBJECTIVE
OBJECTIVE
This review aims to bridge the knowledge gap regarding the immunogenic mechanisms of BoNT-A and to explore effective management strategies to mitigate these immune responses.
MATERIALS AND METHODS
METHODS
The authors conducted a systematic search in databases including PubMed, Embase, and Web of Science, using keywords related to BoNT-A's immunogenicity. The selection process refined 157 initial articles down to 23 relevant studies, which underwent analysis to investigate the underlying mechanisms of immunogenicity and the factors influencing it.
RESULTS
RESULTS
The analysis revealed that both the neurotoxin component and the neurotoxin-associated proteins could elicit an immune response. However, only antibodies against the core toxin influence therapeutic outcomes. Various patient-specific factors such as genetic predispositions and prior immune experiences, along with treatment-related factors such as dosage and frequency, play crucial roles in shaping these responses.
CONCLUSION
CONCLUSIONS
Understanding the specific immunogenic triggers and responses to BoNT-A is critical for optimizing treatment protocols and improving patient outcomes.
Identifiants
pubmed: 39196845
doi: 10.1097/DSS.0000000000004293
pii: 00042728-202409001-00023
doi:
Substances chimiques
Botulinum Toxins, Type A
EC 3.4.24.69
Neuromuscular Agents
0
Antibodies, Neutralizing
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
S117-S126Informations de copyright
Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
Références
Rahman E, Banerjee PS, Asghar A, Gupta NK, et al. Botulinum toxin type A immunogenicity across multiple indications: an overview systematic review. Plast Reconstr Surg 2022;149:837–48.
Rahman E, Alhitmi HK, Mosahebi A. Immunogenicity to botulinum toxin type A: a systematic review with meta-analysis across therapeutic indications. Aesthet Surg J 2022;42:106–20.
Mathevon L, Declemy A, Laffont I, Perennou D. Immunogenicity induced by botulinum toxin injections for limb spasticity: a systematic review. Ann Phys Rehabil Med 2019;62:241–51.
Lacroix-Desmazes S, Mouly S, Popoff MR, Colosimo C. Systematic analysis of botulinum neurotoxin type A immunogenicity in clinical studies. Basal Ganglia 2017;9:12–7.
Fabbri M, Leodori G, Fernandes RM, Bhidayasiri R, et al. Neutralizing antibody and botulinum toxin therapy: a systematic review and meta-analysis. Neurotox Res 2016;29:105–17.
Jankovic J, Carruthers J, Naumann M, Boodhoo T, et al. Neutralizing antibody conversion with onabotulinumtoxinA from global studies across multiple indications in nearly 30,000 patient records: a meta-analysis. Toxicon 2021;190:S35.
Matucci A, Nencini F, Vivarelli E, Bormioli S, et al. Immunogenicity-unwanted immune responses to biological drugs–can we predict them? Expert Rev Clin Pharmacol 2021;14:47–53.
Blattner CM, Chaudhari SP, Young J, Murase JE. A dermatologist guide to immunogenicity. Int J Womens Dermatol 2016;2:77–84.
Benecke R. Clinical relevance of botulinum toxin immunogenicity. BioDrugs 2012;26:e1–e9.
Mejia NI, Vuong KD, Jankovic J. Long-term botulinum toxin efficacy, safety, and immunogenicity. Mov Disord 2005;20:592–7.
Martin MU, Frevert J, Tay CM. Complexing protein-free botulinum neurotoxin A formulations: implications of excipients for immunogenicity. Toxins (Basel). 2024;16:101.
Bellows S, Jankovic J. Immunogenicity associated with botulinum toxin treatment. Toxins (Basel). 2019;11:491.
Naumann M, Boo LM, Ackerman AH, Gallagher CJ. Immunogenicity of botulinum toxins. J Neural Transm (Vienna) 2013;120:275–90.
Critchfield J, Sanders ME, Setler PE. Immunogenicity of botulinum toxin therapy. CNS Spectr 2000;5:s1–s8.
Shtefan V, Fletcher J, Duclos OA. Causes of botulinum toxin treatment failure. Clin Cosmet Investig Dermatol 2022;15:1045–9.
Carr WW, Jain N, Sublett JW. Immunogenicity of botulinum toxin formulations: potential therapeutic implications. Adv Ther 2021;38:5046–64.
Costa J, Espírito-Santo Cláudia C, Borges ANA, Ferreira J, et al. Botulinumtoxin type A therapy for blepharospasm(Review). Cochrane Database Syst Rev 2009.
Park JY, Corduff N, Frevert J, Wanitphakdeedecha R, et al. Immunogenicity associated with aesthetic Botulinumtoxin A: a survey of asia-pacific physicians' experiences and recommendations. Plast Reconstr Surg Glob Open 2022;10:e4217.
Stephan F, Habre M, Tomb R. Clinical resistance to three types of botulinum toxin type A in aesthetic medicine. J Cosmet Dermatol 2014;13:346–8.
Frevert J. Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type A products. Drugs R&D 2015;15:1–9.
Park JY, Sunga O, Wanitphakdeedecha R, Frevert J. Neurotoxin impurities: a review of threats to efficacy. Plast Reconstr Surg Glob Open 2020;8:e2627.
Dashtipour K, Pedouim F. Botulinum toxin: preparations for clinical use, immunogenicity, side effects, and safety profile. Semin Neurol 2016;36:29–33.
Gallagher CJ, Bowsher RR, Clancy A, Dover JS, et al. Clinical immunogenicity of DaxibotulinumtoxinA for injection in glabellar lines: pooled data from the SAKURA phase 3 trials. Toxins (Basel) 2023;15:60.
Pratt KP. Engineering less immunogenic and antigenic FVIII proteins. Cell Immunol 2016;301:12–7.
Kutschenko A, Bigalke H, Wegner F, Wohlfarth K. The role of human serum albumin and neurotoxin associated proteins in the formulation of BoNT/A products. Toxicon 2019;168:158–63.
Kukreja R, Chang TW, Cai S, Lindo P, et al. Immunological characterization of the subunits of type A botulinum neurotoxin and different components of its associated proteins. Toxicon 2009;53:616–24.
Ramirez-Castaneda J, Jankovic J. Long-term efficacy and safety of botulinum toxin injections in dystonia. Toxins (Basel). 2013;5:249–66.
Pittman PR, Hack D, Mangiafico J, Gibbs P, et al. Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid. Vaccine 2002;20:2107–15.
Dressler D. Clinical presentation and management of antibody-induced failure of botulinum toxin therapy. Mov Disord 2004;19(Suppl 8):S92–S100.
Allergan. Botox Package Insert. Irvine, CA: Allergan, Inc; 1–37. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103000s5302lbl.pdf (2017).
Trindade De Almeida AR, Secco LC, Carruthers A. Handling botulinum toxins: an updated literature review. Dermatol Surg 2011;37:1553–65.
Gartlan MG, Hoffman HT. Crystalline preparation of botulinum toxin type A (Botox): degradation in potency with storage. Otolaryngol-Head Neck Surg 1993;108:135–40.
Sharma SK, Fu FN, Singh BR. Molecular properties of a hemagglutinin purified from type A Clostridium botulinum. J Protein Chem 1999;18:29–38.
Wang L, Sun Y, Yang W, Lindo P, et al. Type A botulinum neurotoxin complex proteins differentially modulate host response of neuronal cells. Toxicon 2014;82:52–60.
Jankovic J, Schwartz K. Response and immunoresistance to botulinum toxin injections. Neurology 1995;45:1743–6.
Fogdell-Hahn A. Antidrug antibodies: B cell immunity against therapy. Scand J Immunol 2015;82:184–90.
Zandvliet ML, van Bezooijen JS, Bos MA, Prens EP, et al. Monitoring antigen-specific biologics: current knowledge and future prospects. Ther Drug Monit 2013;35:588–94.
Chen F, Kuziemko GM, Amersdorfer P, Wong C, et al. Antibody mapping to domains of botulinum neurotoxin serotype A in the complexed and uncomplexed forms. Infect Immun 1997;65:1626–30.
Levy R, Forsyth CM, LaPorte SL, Geren IN, et al. Fine and domain-level epitope mapping of botulinum neurotoxin type A neutralizing antibodies by yeast surface display. J Mol Biol 2007;365:196–210.
Scotcher MC, McGarvey JA, Johnson EA, Stanker LH. Epitope characterization and variable region sequence of F1-40, a high-affinity monoclonal antibody to botulinum neurotoxin type A (Hall strain). PLoS One 2009;4:e4924.
Costa Del Amo P, Lahoz-Beneytez J, Boelen L, Ahmed R, et al. Human T SCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness. Plos Biol 2018;16:e2005523.
Adams NM, O'Sullivan TE, Geary CD, Karo JM, et al. NK cell responses redefine immunological memory. J Immunol (Baltimore, Md, 1950) 2016;197:2963–70.
MacKay LK, Rahimpour A, Ma JZ, Collins N, et al. The developmental pathway for CD103+ CD8+ tissue-resident memory T cells of skin. Nat Immunol 2013;14:1294–301.
Khalil S, Bardawil T, Kurban M, Abbas O. Tissue-resident memory T cells in the skin. Inflamm Res 2020;69:245–54.
Herrmann J, Geth K, Mall V, Bigalke H, et al. Clinical impact of antibody formation to botulinum toxin A in children. Ann Neurol 2004;55:732–5.
Oshima M, Deitiker P, Jankovic J, Atassi MZ. The regions on the light chain of botulinum neurotoxin type A recognized by T cells from toxin-treated cervical dystonia patients. The complete human T-cell recognition map of the toxin molecule. Immunol Invest 2018;47:18–39.
Solberg OD, Mack SJ, Lancaster AK, Single RM, et al. Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies. Hum Immunol 2008;69:443–64.
Schulte-Baukloh H, Bigalke H, Miller K, Heine G, et al. Botulinum neurotoxin type A in urology: antibodies as a cause of therapy failure. Int J Urol 2008;15:407–15.
Kessler KR, Skutta M, Benecke R. Long-term treatment of cervical dystonia with botulinum toxin A: efficacy, safety, and antibody frequency. German Dystonia Study Group. J Neurol 1999;246:265–74.
Lange O, Bigalke H, Dengler R, Wegner F, et al. Neutralizing antibodies and secondary therapy failure after treatment with botulinum toxin type A: much ado about nothing? Clin Neuropharmacol 2009;32:213–8.
Colosimo C, Tiple D, Berardelli A. Efficacy and safety of long-term botulinum toxin treatment in craniocervical dystonia: a systematic review. Neurotox Res 2012;22:265–73.
Ceballos-Baumann AO, Sheean G, Passingham RE, Marsden CD, et al. Botulinum toxin does not reverse the cortical dysfunction associated with writer's cramp. A PET study. Brain a J Neurol 1997;120(Pt 4):571–82.
Gilio F, Currà A, Lorenzano C, Modugno N, et al. Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia. Ann Neurol 2000;48:20–6.
Kim DY, Oh BM, Paik NJ. Central effect of botulinum toxin type A in humans. Int J Neurosci 2006;116:667–80.
Diggle L, Deeks JJ, Pollard AJ. Effect of needle size on immunogenicity and reactogenicity of vaccines in infants: randomised controlled trial. BMJ 2006;333:571.
Kumar S, Jeong Y, Ashraf MU, Bae YS. Dendritic cell-mediated th2 immunity and immune disorders. Int J Mol Sci 2019;20:2159.
Fabi SG, Park JY, Goldie K, Wu W. Microtoxin for improving pore size, skin laxity, sebum control, and scars: a roundtable on integrating intradermal botulinum toxin type A microdoses into clinical practice. Aesthet Surg J 2023;43:1015–24.
Atwa EM, Nasr MM, Ebrahim HM. Evaluation of intradermal injection of botulinum toxin A for facial lifting. J Clin Aesthet Dermatol 2020;13:22–6.
Jun JY, Park JH, Youn CS, Lee JH. Intradermal injection of botulinum toxin: a safer treatment modality for forehead wrinkles. Ann Dermatol 2018;30:458–61.
Shah AR. Use of intradermal botulinum toxin to reduce sebum production and facial pore size. J Drugs Dermatol JDD 2008;7:847–50.
Zhu J, ji X, Xu Y, Liu J, et al. The efficacy of intradermal injection of type A botulinum toxin for facial rejuvenation. Dermatol Ther 2017;30:e12433.
Kim YJ, Lim OK, Choi WJ. Are there differences between intradermal and intramuscular injections of botulinum toxin on the forehead? Dermatol Surg 2020;46:e126–e131.
Wanitphakdeedecha R, Yan C, Apinuntham C, Rojanavanich V, et al. Intradermal micro-dosing of AbobotulinumtoxinA for face-lifting: how long does it last? Dermatol Ther (Heidelb) 2020;10:779–89.
An WF, Tolliday N. Cell-based assays for high-throughput screening. Mol Biotechnol 2010;45:180–6.
Jankovic J, Carruthers J, Naumann M, Ogilvie P, et al. Neutralizing antibody formation with OnabotulinumtoxinA (BOTOX®) treatment from global registration studies across multiple indications: a meta-analysis. Toxins (Basel) 2023;15:342.
Gallagher CJ, Bowsher RR, Clancy A, et al. Immunogenicity of DaxibotulinumtoxinA for injection in glagellar lines: pooled data from the SAKURA phase 3 trials. Toxins (Basel). 2023;15(1):1–13.
Fabbri M, Leodori G, Fernandes RM. Neutralizing antibody and botulinum toxin therapy: a systematic review and meta-analysis. Neurotox Res. 2015;29(1):105–117.