Neutralizing Antibodies to Botulinum Toxin Type A as a Secondary Treatment Failure: A Case Report from Mumbai, India
DOI:
https://doi.org/10.17140/TCOJ-5-117Keywords:
Botulinum neurotoxin type A, Neutralizing antibodies, Secondary treatment failure, Aesthetic treatment, Facial rhytidesAbstract
Botulinum toxin use in aesthetic medicine for treatment of facial rhytids is common and has become more and more popular in India in recent times. Botulinum toxin (BoNT) is produced by clostridium botulinum which is an anaerobic, spore forming, rod shaped bacteria. The botulinum toxin complex contains a 150 KD neurotoxin together with a complex additional protein. The neurotoxin is cleaved by the clostridial proteases into heavy and light chain. The heavy chain (100 KD) after cleavage binds to gangliosides and a protein receptor on the presynaptic nerve ending, whereas the light chain (50 KD) blocks the release of acetyl choline, leading to a dose dependent weakening of the target muscle.
References
Eisele KH, Fink K, Vey M, Taylor HV. Studies on the dissocia-tion of botulinum neurotoxin type A complexes. Toxicon. 2011; 57: 555-565. doi: 10.1016/j.toxicon.2010.12.019
Frevert J, Dressler D. Complexing proteins in botulinum toxin type A drugs: A help or a hindrance? Biologics. 2010; 4: 325-332. doi: 10.2147/BTT.S14902
Kukreja RV, Singh BR. Comparative role of neurotoxin associ-ated proteins in the structural stability and endopeptidase activity of botulinum neurotoxin complex type A and E. Biochemistry. 2007; 46: 1416-14324. doi: 10.1021/bi701564f
Dong M, Yeh F, Tepp WH, et al. SV2 Is the protein receptor for botulinum neurotoxin A. Science. 2006; 312: 592-596. doi: 10.1126/ science.1123654
Pirrazini M, Rossetto O, Eleopra R, Montecucco C. Botulinum neurotoxins: Biology, pharmacology, and toxicology. Pharmacol. Rev. 2017; 69: 200-235. doi: 10.1124/pr.116.012658
Dressler D, Bigalke H. Immunological aspects of botuli-num toxin therapy. Expert Rev Neurother. 2017; 17: 487-494. doi: 10.1080/14737175.2017.1262258
Ojo OO, Fernandez HH. Is it time for flexibility in Botulinum inter-injection intervals? Toxicon. 2015; 107: 72-76. doi: 10.1016/j. toxicon.2015.09.037
Sethi KD, Rodriguez R, Olayinka B. Satisfaction with Botu-linum toxin treatment: A cross sectional survey of patients with cervical dystonia. J. Med. Econ. 2012; 15: 419-423. doi: 10.3111/13696998.2011.653726
Evidente VGH, Fernandez HH, LeDoux MS, et al. A ran-domised, double blind study of repeated Incobotulinumtoxin A(Xeonim(®))in cervical dystonia. J Neural Transm (Vienna). 2013; 120: 1699-1707. doi: 10.1007/s00702-013-1048-3
Truong DD, Gollomp SM, Jankovic J, LeWitt PA, Marx M, Hanschmann A, Fernandez HH, Xeomin US Blepharospasm study group. Sustained efficacy and safety of repeated Incobotulinum-toxin A (Xeonim(®)) injections in blepharospasm. J Neural Transm (Vienna). 2013; 120: 1345-1353. doi: 10.1007/s00702-013-0998-9
Kukreja R, Chang TW, Cai S, et al. Immunological characteriza-tion of the subunits of type A botulinum neurotoxin and different components of its associated proteins. Toxicon. 2009; 53: 616-624. doi: 10.1016/j.toxicon.2009.01.017
Torji Y, Goto Y Nakahira S, Kozaki S, Ginnaga A. Comparison of the immunogenicity of botulinum type A and the efficacy of A1 and A2 neurotoxins in animals with A1 toxin antibodies. Toxi-con. 2014; 77: 114-120. doi: 10.1016/j toxin.2013.11.006
Dressler D, Wohlfabrt K, Rogge E, Wiest L, Bigalke H. An-tibody induced failure of botulinum toxin a therapy in cosmet-ic indications. Dematol Surg. 2010; 36 (supply 4): 2182-2187. doi: 10.1111/j,1524-4725. 2010.01710.x
Dressler D, Pan L, Adib Saberi F. Antibody induced failure of toxin therapy: Re-start with low antigenicity drugs offers a new treatment opportunity. J Neural Transm (Vienna). 2018; 125: 1481- 1486. doi: 10.1007/s00702-018-1911-3
Stengel G, Bee EK. Antibody induced secondary treatment failure in a patient treated with botulinum toxin type A for glabel-lar frown lines. Clin Interv Aging. 2011; 6: 281-284. doi: 10.2147/ CIA. S18997
Shulte-Baukloh H, Bigalke H, Miller K, et al. Botulinum toxin type a in urology: Antibodies as a cause of therapy failure. Int J Urol. 2008; 15: 407-415: discussion 415. doi: 10.1111/j.1442- 2042.2008.02016x
Yablon SA, Brashear A, Gordon MF, Elovic EP. Formation of neutralizing antibodies in patients receiving botulinum toxin type A for treatment of post stroke spasticity: A pooled data analysis of three clinical trials. Clin Ther. 2007; 29: 683-690. doi: 10.1016/ jclinthera.2007.04.015
Yablon S. The development of toxin neutralizing antibodies with botulinum toxin type A (botulinum toxin type A) treatment. Neurotox Res. 2006; 9: 238.
Brin MF, Comella CL, Jankovik J, Lai F, Naumann M, CD-017 BoNTA Study Group. Long term treatment with botulinum tox-in type A in cervical dystonia has low immunogenicity by mouse protection assay. Mov Disord. 2008; 23: 1353-1360. doi: 10.1002/ mds.22157
Muller K, Mix E, Adib Saberi FA, Dressler D, Benecke R. Prev-alence of neutralizing antibodies in patients treated with botuli-num toxin type A for spasticity. J Neural Transm (Vienna). 2009; 116: 579-585. doi: 10.1007/s00702-009.0223-z
Dressler D. Pharmacological aspects of therapeutic botulinum toxin preparations. Nervenarzt. 2006; 77: 912-921. doi: 10.1007/ s00115-006-2090-2
Jankovic J, Vuong KD, Ahsan J. Comparison of efficacy and immunogenicity of original versus current botulinum toxin in cer-vical dystonia. Neurology. 2003; 60: 1186-1188. doi: 10.1212/01. wnl.0000055087.96356bb
Torres S, Hamilton M, Sanches E, Starovatova P, Gubanova E, Reshetnikova T. Neutralizing antibodies to botulinum toxin type A in aesthetic medicine: Five case reports. Clin Cosmet Investig Derma-tol. 2014; 7: 11-17. doi: 10.2147/CCID,S51938
Dashtipour K, Pedouim F. Botulinum toxin: Preparations for clinical use, immunogenicity, side effects, and safety profile. Semin Neurol. 2016; 36: 29-33. doi: 10.1055/s-0035-1571213
Samizadeh S, De Boulle K. Botulinum neurotoxin formula-tions: Overcoming the confusion. Clin Cosmet Investig Dermatol. 2018; 11: 273-287. doi: 10.2147/CCID.S156851
Goschel H, Wohlfarth K, Frevert J, Dengler R, Bigalke H. Bot-ulinum A toxin therapy: Neutralizing and non neutralizing anti-bodiies- therapeutic consequences. Exp Neurol. 1997; 147: 96-102. doi: 10.1006/exnr.1997.6580
Nauman M, Boo LM, Ackerman AH, Gallagher CJ. Immuno-genicity of botulinum toxins. J Neural Transm (Vienna). 2013; 120: 275-290. doi: 10.1007/s00702-012-0893-9 Case Report | Volume 5 | Issue 1 | Khatri NM, et al
Hsiung GYR, Das SK, Ranawaya R, Lafontain AL, Suchow-ersky O. Long term efficacy of botulinum toxin A in treatment of various movement disorders over a 10 year period. Mov Disord. 2002; 17: 1288-1293. doi: 10.1002/mds.10252
Ramirez-Castaneda J, Jankovic J. Long term efficacy and safety of botulinum toxin injections in Dystonia. Toxins (Basel). 2013; 5: 249-266. doi: 10.3390/toxins5020249
Jinnah HA, Goodman E, Rosen AR, Evatt M, Freeman A, Factor S. Botulinum toxin treatment failures in cervical dystonia: Causes management and outcomes. J Neurol. 2016; 263: 1188-1194. doi: 10.1007/s00415-016-8136-x
Fabbri M, Leodori G, Fernandes RM, et al. Neutralizing anti-body and botulinum toxin therapy: Systematic review and meta-analysis. Neurotox Res. 2016; 29: 105-117. doi: 10.1007/s12640-015- 9565-5
Oshima M, Deitiker P, Jankovic J, Attasi MZ. The regions on the light chain of botulinum toxin type A recognised by T cells from toxin related cervical dystonia patients. The complete hu-man T cell recognition map of the toxin molecule. Immunol Investig. 2018; 47: 18-39. doi: 10.1080/08820139.2017.1368544
Dolimbek BZ, Steward LE, Aoki KR, Attasi MZ. Location of the synaptosome binding regions on botulinum toxin B. Biochemis-try. 2012; 51: 316-328. doi: 10.1021/bi201322c
Sankhla C, jankovic J, Duane D. Variability of the immunologic and clinical response in dystonic patients immunoresistant to botu-linum toxin injections. Mov Disord. 1998; 13: 150-154. doi: 10.1002/ mds.870130128
Dressler D, Pan L, Adib Saberi F. Antibody induced failure of botulinum toxin therapy: Re-start with low antigenicity drugs of-fers a new treatment opportunity. J Neural Transm (Vienna). 2018; 125: 1481-1486. doi: 10.1007/s00702-018-1911-3
Dressler D, Munchau A, Bhatia KP, Quinn NP, Bigalke H. An-tibody induced botulinum toxin therapy failure: Can it be over-come by increased botulinum toxin doses? Eur Neurol. 2002; 47: 118-121. doi: 10.1159/000047963
Joshi SG, Elias M, Singh A, et al. Modulation of botulinum toxin induced changes in neuromuscular function with antibodies directed against recombinant polypeptides or fragments. Neurosci-ence. 2011; 179: 208-222. doi: 10.1016/j.neuroscience.2011.01.033
Aoki KR, Guyer B. Botulinum toxin type A and other botu-linum toxin serotypes: A comparative review of biochemical and pharmacological actions. Eur J Neurol. 2001; 8 (Suppl.5): 21-29. doi: 10.1046/j.1468-1331.2001.00035.x
Dressler D, Hallet M. Immunological aspects of botox, dysport and myobloc/neurobloc. Eur J Neurol. 2006; 13 (Suppl. 1): 11-15. doi: 10.1111/j.1468-1331.2006.01439.x
Hanna PA, Jankovic J, Vincent A. Comparison of mouse bio-assay and immunoprecipitation assay for botulinum toxin antibod-ies. J Neurol Neurosurg Psychiatry. 1999; 66: 612-616. doi: 10.1136/ jnnp.66.5.612
Hanna PA, Jankovic J. Mouse bioassay versus western blot assay for botulinum toxin antibodies: Correlation with clinical response. Neurology. 1998; 50(6): 1624-1629. doi: 10.1212/wnl.50.6.1624
Dressler D. Clinical presentation and management of antibody-induced failure of botulinum toxin therapy. Mov Disord. 2004; 19 suppl 8: S92-S100. doi: 10.1002/mds.20022
Borodic G. Immunologic resistance after repeated botulinum toxin type A injections for facial rhytides. Ophthal Plast Reconsr. 2006; 22: 239-240. doi: 10.1097/01.iop.0000217703.80859.a3
Lee SK. Antibody-induced failure of botulinum toxin type A therapy in a patient with massetric hypertrophy. Dermatol Surg. 2007; 33 (1 Spec No): S105-S110. doi: 10.1111/j.1524-4725.2006.32340.x
Dressler D, Wohlfahrt K, Mever-Rogg E, Bigalke H. Antibody-Submit your article to this journal | https://openventio.org/submit-manuscript/ induced failure of botulinum toxin type A therapy in cosmetic indications. Dermatol Surg. 2010; 36 Suppl 4: 2182-2187. doi: 10.1111/j.1524-4725.2010.01710.x
Stengel G, Bee EK. Antibody-induced secondary treatment failure in a patient treated with botulinum toxin type A for glabel-lar frown lines. Clin Interv Aging. 2011; 6: 281-284. doi: 10.2147/ CIA.S18997
Mohammadi B, Buhr N, Bigalke H, Krampfl K, Del-ger R, Kollewe K. A long term follow up of botulinum tox-in A in cervical dystonia. Neurol Res. 2009; 31: 463-466. doi: 10.1179/174313209X405137
Nauman M, Carruthers A, Carruthers J, et al. Meta analysis of neutralizing antibody conversion with onabotulinum toxin A (BO-TOX®) across multiple indications. Mov Disord. 2010; 25: 2211- 2218. doi: 10.1002/mds.23254
Frevert J. Pharmacological, biological and clinical properties of botulinum neurotoxin type A products. Drugs R D. 2015; 15(1): 1-9. doi: 10.1007/s40268-014-0077-1
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Trichology and Cosmetology (TC) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.