Basic immunological aspects of botulinum toxin therapy.
Identifieur interne : 000D75 ( Ncbi/Checkpoint ); précédent : 000D74; suivant : 000D76Basic immunological aspects of botulinum toxin therapy.
Auteurs : M Zouhair Atassi [États-Unis]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2004.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies (immunology), Botulinum Toxins (immunology), Botulinum Toxins (therapeutic use), Cross Reactions, Epitope Mapping, Humans, Immunization (methods), Immunotherapy, Neurotoxins (immunology), Neurotoxins (therapeutic use), Peptide Fragments (chemistry), Peptide Fragments (immunology), Tetanus Toxin (immunology), Time Factors.
- MESH :
- chemical , chemistry : Peptide Fragments.
- chemical , immunology : Antibodies, Botulinum Toxins, Neurotoxins, Peptide Fragments, Tetanus Toxin.
- chemical , therapeutic use : Botulinum Toxins, Neurotoxins.
- methods : Immunization.
- Amino Acid Sequence, Animals, Cross Reactions, Epitope Mapping, Humans, Immunotherapy, Time Factors.
Abstract
Previous studies in this laboratory had mapped the immune recognition profile of the regions recognized antibodies (Abs) and by T cells on the protective H(C) domain (C-terminal fragment corresponding to residues 855-1296 of the heavy chain) of botulinum neurotoxin serotype A (BoNT/A). The localization of these regions has several potential applications and has provided a basis for the understanding of immunoresistance to treatment. We briefly outline these localized regions and discuss the impact of these findings on the immunotherapeutic applications of BoNT/A. Immunoresistance to toxin therapy can appear in some patients after a few injections with the toxin. Our epitope mapping studies have shown that several factors can influence the immune response to the toxin. These factors include dose, duration of treatment, frequency of immunization, and quality of the toxin. The immune response to the whole toxin is under genetic control, and the response to each epitope is under separate genetic control. Therefore, the appearance of blocking Abs (i.e., immunoresistance) in patients might be controlled by the major histocompatability of the host. Once a patient becomes immunoresistant to one toxin then switching to another toxin will most often be of limited and short-lived benefit, because the patient becomes rapidly immunoresistant to the second toxin. Finally, because of the considerable structural homology between tetanus neurotoxin (TeNT) and BoNTs, it is possible, although not certain, that a prior active immune response to TeNT might play some role in the early appearance on anti-BoNT Abs in some patients.
DOI: 10.1002/mds.20020
PubMed: 15027058
Affiliations:
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<affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. matassi@bcm.tmc.edu</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030</wicri:regionArea>
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<term>Botulinum Toxins (immunology)</term>
<term>Botulinum Toxins (therapeutic use)</term>
<term>Cross Reactions</term>
<term>Epitope Mapping</term>
<term>Humans</term>
<term>Immunization (methods)</term>
<term>Immunotherapy</term>
<term>Neurotoxins (immunology)</term>
<term>Neurotoxins (therapeutic use)</term>
<term>Peptide Fragments (chemistry)</term>
<term>Peptide Fragments (immunology)</term>
<term>Tetanus Toxin (immunology)</term>
<term>Time Factors</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Peptide Fragments</term>
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<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies</term>
<term>Botulinum Toxins</term>
<term>Neurotoxins</term>
<term>Peptide Fragments</term>
<term>Tetanus Toxin</term>
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<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Botulinum Toxins</term>
<term>Neurotoxins</term>
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<term>Cross Reactions</term>
<term>Epitope Mapping</term>
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<front><div type="abstract" xml:lang="en">Previous studies in this laboratory had mapped the immune recognition profile of the regions recognized antibodies (Abs) and by T cells on the protective H(C) domain (C-terminal fragment corresponding to residues 855-1296 of the heavy chain) of botulinum neurotoxin serotype A (BoNT/A). The localization of these regions has several potential applications and has provided a basis for the understanding of immunoresistance to treatment. We briefly outline these localized regions and discuss the impact of these findings on the immunotherapeutic applications of BoNT/A. Immunoresistance to toxin therapy can appear in some patients after a few injections with the toxin. Our epitope mapping studies have shown that several factors can influence the immune response to the toxin. These factors include dose, duration of treatment, frequency of immunization, and quality of the toxin. The immune response to the whole toxin is under genetic control, and the response to each epitope is under separate genetic control. Therefore, the appearance of blocking Abs (i.e., immunoresistance) in patients might be controlled by the major histocompatability of the host. Once a patient becomes immunoresistant to one toxin then switching to another toxin will most often be of limited and short-lived benefit, because the patient becomes rapidly immunoresistant to the second toxin. Finally, because of the considerable structural homology between tetanus neurotoxin (TeNT) and BoNTs, it is possible, although not certain, that a prior active immune response to TeNT might play some role in the early appearance on anti-BoNT Abs in some patients.</div>
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