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J Neurol Neurosurg Psychiatry 1999;66:612-616 ( May )

Comparison of mouse bioassay and immunoprecipitation assay for botulinum toxin antibodies

Philip A Hanna,a Joseph Jankovic,a Angela Vincentb

a Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA, b Neurosciences Group, Department of Clinical Neurology, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford UK

Correspondence to: Dr Joseph Jankovic, Department of Neurology, Director of Parkinson's Disease Center, and Movement Disorders Clinic, Baylor College of Medicine, 6550 Fannin St No 1801, Houston, Texas 77030, USA. Telephone 001 713 798 5998; fax 001 713 798 6808.

Received 27 August 1998 and in revised form 16 November 1998; Accepted 26 November 1998

OBJECTIVE---To compare a recently developed immunoprecipitation assay (IPA) to the mouse protection bioassay (MPB), currently considered the "gold standard", for detecting antibodies against botulinum toxin A (BTX-A) and to correlate these assay results with clinical responses to BTX-A injections.
METHODS---MPB and IPA assays were performed on serum samples from 83 patients (38 non-responders, 45 responders) who received BTX-A injections. Six non-responders had serum tested on two separate occasions. Some patients also received a "test" injection into either the right eyebrow (n=29) or right frontalis (n=19).
RESULTS---All patients antibody positive (Ab+) by MPB were also Ab+ by IPA, whereas an additional 19 patients (17 with reduced or no clinical response) who were MPB Ab- were Ab+, with low titres, by IPA. Two of these 19 patients (non-responders) were initially MPB Ab- but later became MPB Ab+. Similar to previous studies, the sensitivity for the MPB was low; 50% for clinical, 38% for eyebrow, and 30% for frontalis responses whereas the IPA sensitivity was much higher at 84% for clinical (p<0.001), 77% for eyebrow (p=0.111, NS) and 90% for frontalis responses (p<0.02). The IPA specificity was 89% for clinical, 81% for eyebrow, and 89% for frontalis responses, whereas the MPB specificity was 100% for all three response types, which were all non-significant differences.
CONCLUSIONS---Both assays had high specificity although the sensitivity of the IPA was higher than the MPB. In addition, the IPA seems to display positivity earlier than the MPB, and as such, it may prognosticate future non-responsiveness. Eyebrow and frontalis "test" injections correlated well with clinical and immunological results and are useful in the assessment of BTX non-responders.


Keywords: dystonia; botulinum toxin; antibodies; immunoresistance


© 1999 by Journal of Neurology, Neurosurgery, and Psychiatry



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