Basic immunological aspects of botulinum toxin therapy.
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.
Atassi
M Zouhair
MZ
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. matassi@bcm.tmc.edu
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001905:Botulinum Toxins / Q000276:immunology* / Q000627:therapeutic use; D003429:Cross Reactions; D018604:Epitope Mapping; D006801:Humans; D007114:Immunization / Q000379:methods; D007167:Immunotherapy; D009498:Neurotoxins / Q000276:immunology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D013744:Tetanus Toxin / Q000276:immunology; D013997:Time Factors
D000906:Antibodies; D009498:Neurotoxins; D010446:Peptide Fragments; D013744:Tetanus Toxin; D001905:Botulinum Toxins