Antibody responses to botulinum neurotoxin type A of toxin-treated spastic equinus children with cerebral palsy: A randomized clinical trial comparing two injection schedules

- Studied Ab response link to HLA in toxin-naïve spastic equines children with cerebral palsy treated with BoNT/A tri-annually or annually.
- Blocking Abs detected in 2 out of 18 sera samples in the tri-annual group but none in 20 samples from the annual group.
- The blocking Abs positive sera samples gave in RIA higher anti-BoNT/A Ab-binding levels than the negative samples.
- Higher Ab binding in RIA correlating with blocking Abs in two samples in the tri-annual group.
- By combining data from CD studies, association between DQB1*06:04 and DQA1*01:02 and Ab-positivity was significant.

We have conducted a 26-month-long comparative study involving young patients (2-6 years 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.

122