Injections of Clostridium botulinum neurotoxin A may cause thyroid complications in predisposed persons based on molecular mimicry with thyroid autoantigens.
A woman with Hashimoto's thyroiditis, under replacement L-T4, repeatedly experienced, over a 10-year period, elevations of serum TSH after eyelid injections of Clostridium botulinum neurotoxin A (Btx). We hypothesized a link between Btx injections and TSH elevations via molecular mimicry, and aimed to verify our hypothesis. Using an in silico approach, we searched first for amino acid sequence homology between Btx and thyroid autoantigens, and next for HLA binding motifs within homologous segments. We found that (i) Btx and thyroid autoantigens share amino acid sequence homology; (ii) some homologous regions contain epitopes of both Btx and thyroid autoantigens; (iii) some of such regions contain HLA-DR3 and/or HLA-DR7 binding motifs, which predominate over other HLA-DRs. This is relevant because the patient's HLA-DR haplotype was DR3/DR7. In conclusion, clinical and bioinformatics data suggest a possible pathogenetic link between Btx and autoimmune thyroid diseases. Considering the wide and increasing medical and dermocosmetic use of Btx, and the frequently subclinical course of autoimmune thyroid diseases, we think that thyroid "complications" may pass frequently undetected in Btx-treated persons.
Department of Nuclear Medicine, Hospital Izola, Izola, Slovenia.
Edvina
E
Gregoric
Jurji Avramovic
JA
Gregoric
Fabrizio
F
Guarneri
Salvatore
S
Benvenga
D000368:Aged; D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D001665:Binding Sites; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D005143:Eyelids / Q000187:drug effects; D005260:Female; D015803:HLA-DR3 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015809:HLA-DR7 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D050031:Hashimoto Disease / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007267:Injections; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013961:Thyroid Gland / Q000276:immunology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use
D001324:Autoantigens; D015803:HLA-DR3 Antigen; D015809:HLA-DR7 Antigen; D013972:Thyrotropin; D019274:Botulinum Toxins, Type A; D013974:Thyroxine