title: Antibody responses to botulinum neurotoxin type A of toxin-treated spastic equinus children with cerebral palsy: A randomized clinical trial comparing two injection schedules.
abstract: We have conducted a 26-month-long comparative study involving young patients (2-6years old) with a clinical diagnosis of spastic equinus secondary to cerebral palsy who have been treated with BoNT/A (BOTOX®, Allergan) tri-annually or annually. Serum samples were obtained to determine the presence or absence of blocking antibodies (Abs) by a mouse protection assay (MPA) and levels of anti-BoNT/A Abs by radioimmune assay (RIA). HLA DQ alleles were typed using blood samples to determine the possible association of certain HLA type(s) with the disease or with the Ab status. Blocking Abs were detected in only two out of 18 serum samples of the tri-annual group, but none were found in 20 samples of the annual group. The MPA-positive serum samples gave in RIA significantly higher anti-BoNT/A Ab-binding levels than the MPA-negative samples. On the other hand, when two MPA-positive sample data were excluded, serum samples from tri-annual and annual groups showed similar anti-BoNT/A Ab levels. Linkage of the disorder with a particular HLA DQA1 and DQB1 allele types was not observed due to the small sample size. However, by combining results with other studies on BoNT/A-treated Caucasian patients with cervical dystonia (CD), we found that, among Caucasian patients treated with BoNT/A, DQA1*01:02 and DQB1*06:04 were higher in Ab-positive than in Ab-negative patients. The genetic linkage was on the threshold of corrected significance.
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Minako
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Deitiker
authors.affiliation: NHMRC-Funded Centre of Research Excellence in Cerebral Palsy, Melbourne, Australia.
authors.forename: Tandy
authors.initials: T
authors.lastname: Hastings-Ison
authors.affiliation: Allergan Inc., Irvine, CA 92612, USA.
authors.forename: K Roger
authors.initials: KR
authors.lastname: Aoki
authors.affiliation: NHMRC-Funded Centre of Research Excellence in Cerebral Palsy, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Australia.
authors.forename: H Kerr
authors.initials: HK
authors.lastname: Graham
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: matassi@bcm.edu.
authors.forename: M Zouhair
authors.initials: MZ
authors.lastname: Atassi
mesh_terms: D065087:Acetylcholine Release Inhibitors; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects*; D019274:Botulinum Toxins, Type A / Q000276:immunology* / Q000627:therapeutic use*; D002547:Cerebral Palsy / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D009128:Muscle Spasticity / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D010597:Pharmacogenetics; D011863:Radioimmunoassay
chemical_list: D065087:Acetylcholine Release Inhibitors; D019138:Antibodies, Blocking; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; D019274:Botulinum Toxins, Type A
keywords: Antibody; Botulinum neurotoxin type A; Cerebral palsy; HLA association; Spastic equinus