title: Evaluation of specific immune responses to BoNT/A and tetanus toxoid in patients undergoing treatment for neurologic disorders.
abstract: Botulinum neurotoxins (BoNTs) are used in the treatment of many neurological disorders. The primary structure of BoNTs shows a high degree of homology with the tetanus neurotoxin, the toxoid of which is used as a vaccine. Because of the potential cross-reactivity between these toxins, we investigated the effects of Botulinum neurotoxin A (BoNT/A) and tetanus toxoid on peripheral blood mononuclear cells (PBMC) and the corresponding serum antibody levels, in twenty patients who had been treated with BoNT/A. We observed very low PBMC immunostimulation by BoNT/A at the tested dose (15 units/ml), as demonstrated by the low lymphocyte proliferation, and the absence of detectable antibodies cross-reacting with tetanus. However, exposure of PBMC from tetanus-sensitized patients to both neurotoxins showed that BoNT/A exerted a co stimulatory effect on tetanus-stimulated cells. Interestingly, in flow cytometry analysis, BoNT/A seemed to also alter the ratio of naïve (CD45RA) : memory/effector (CD45RO) T lymphocyte subsets, in favour of CD45RO. These preliminary data give a new insight on the potential immune crossreactivity between the two antigens. In view of the wide use of both neurotoxins, these immunotoxic effects merit a more detailed investigation.
authors.affiliation: Department of Applied Biochemistry and Immunology, Institute of Molecular Biology and Biotechnology, Vassilika Vouton, Heraklion, Crete, Greece. xvlata@imbb.forth.gr
authors.forename: Zaharenia
authors.initials: Z
authors.lastname: Vlata
authors.forename: Aristidis
authors.initials: A
authors.lastname: Tsatsakis
authors.forename: Minas
authors.initials: M
authors.lastname: Tzagournissakis
authors.forename: Elias
authors.initials: E
authors.lastname: Krambovitis
mesh_terms: D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D057134:Antibodies, Neutralizing / Q000032:analysis / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D001428:Bacterial Vaccines / Q000276:immunology; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003429:Cross Reactions; D045142:Cross-Priming; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007110:Immunity, Active / Q000187:drug effects*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008666:Metalloendopeptidases / Q000276:immunology*; D009422:Nervous System Diseases / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D009498:Neurotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013744:Tetanus Toxin / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D009465:Neuromuscular Agents; D009498:Neurotoxins; D013744:Tetanus Toxin; C035979:tetanospasmin; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D008666:Metalloendopeptidases; D019274:Botulinum Toxins, Type A