{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T06:36:43Z","timestamp":1793860603443,"version":"4.6.1"},"reference-count":141,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merz Asia Pacific Pte., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum Neurotoxin A (BoNT\/A) is a bacterial protein that has proven to be a valuable pharmaceutical in therapeutic indications and aesthetic medicine. One major concern is the formation of neutralizing antibodies (nAbs) to the core BoNT\/A protein. These can interfere with the therapy, resulting in partial or complete antibody (Ab)-mediated secondary non-response (SNR) or immunoresistance. If titers of nAbs reach a level high enough that all injected BoNT\/A molecules are neutralized, immunoresistance occurs. Studies have shown that continuation of treatment of neurology patients who had developed Ab-mediated partial SNR against complexing protein-containing (CPC-) BoNT\/A was in some cases successful if patients were switched to complexing protein-free (CPF-) incobotulinumtoxinA (INCO). This seems to contradict the layperson\u2019s basic immunological understanding that repeated injection with the same antigen BoNT\/A should lead to an increase in antigen-specific antibody titers. As such, we strive to explain how immunological memory works in general, and based on this, we propose a working hypothesis for this paradoxical phenomenon observed in some, but not all, neurology patients with immunoresistance. A critical factor is the presence of potentially immune-stimulatory components in CPC-BoNT\/A products that can act as immunologic adjuvants and activate not only na\u00efve, but also memory B lymphocyte responses. Furthermore, we propose that continuous injection of a BoN\/TA formulation with low immunogenicity, e.g., INCO, may be a viable option for aesthetic patients with existing nAbs. These concepts are supported by a real-world case example of a patient with immunoresistance whose nAb levels declined with corresponding resumption of clinical response despite regular INCO injections.<\/jats:p>","DOI":"10.3390\/toxins16100422","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T03:57:08Z","timestamp":1727841428000},"page":"422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Continuous Treatment with IncobotulinumtoxinA Despite Presence of BoNT\/A Neutralizing Antibodies: Immunological Hypothesis and a Case Report"],"prefix":"10.3390","volume":"16","author":[{"given":"Michael Uwe","family":"Martin","sequence":"first","affiliation":[{"name":"Independent Researcher, 31832 Springe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6720-4154","authenticated-orcid":false,"given":"Clifton Ming","family":"Tay","sequence":"additional","affiliation":[{"name":"Merz Asia Pacific Pte., Ltd., Singapore 138567, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuck Wah","family":"Siew","sequence":"additional","affiliation":[{"name":"Radium Medical Aesthetics, 3 Temasek Boulevard #03-325\/326\/327\/328, Suntec City Mall, Singapore 038983, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1212\/WNL.45.9.1743","article-title":"Response and immunoresistance to botulinum toxin injections","volume":"45","author":"Jankovic","year":"1995","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.1002\/mds.20022","article-title":"Clinical presentation and management of antibody-induced failure of botulinum toxin therapy","volume":"19","author":"Dressler","year":"2004","journal-title":"Mov. 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