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NEUTRALIZING ANTIBODIES IN DYSTONIC PATIENTS WHO STILL RESPOND WELL TO BOTULINUM TOXIN TYPE A
Published 2008 · Medicine
NEUTRALIZING ANTIBODIES IN DYSTONIC PATIENTS WHO STILL RESPOND WELL TO BOTULINUM TOXIN TYPE A To the Editor: Kranz et al. used a ninhydrin sweat test (NST) and mouse diaphragm test (MDT) in 14 dystonic patients and 14 controls and reported subclinical neutralizing antibodies (Abs) in patients with “good clinical responses” to BoNT/A. The authors defined the responses based on a three-point decrease on modified-Tsui scale, injected-muscle atrophy, or reported BoNT/A-associated adverse events.1 Only one patient had anti-BoNT/A Abs (1 mU/mL, by MDT) and a marked anhydrotic area reduction (0.26 cm). Seven other patients had “borderline” titers of either 0.4 or 0.8 mU/mL and reduced anhidrosis area. The study design, small sample size, and subjective clinical-response assessment precludes extension to incidence value ( 40%). Mixing Botoxand Dysport-treated patients complicates analysis because these products have different immune-response rates. NST employs area, but neglects color density. NST correlation value was missing, as the anhydrotic area could vary with injection method. Hyperhidrosis effect reproducibility was also overlooked. The Results imply that NST was done with both Botox and Dysport but this contradicts the statement in the Methods that Dysport was the test agent. The observation that patients had different Ab levels after similar toxin doses is expected.2,3 Immune responses mature with time, boosters, and are genetically controlled.2,3 This means that patients responding to treatment would have different Ab levels, even after similar doses and protocols.2,3 Antibodies are polyclonal. Titer partially affects blocking as recognized epitopes, immunoglobulin class, isotype, and affinity play major roles.3,4 It is unclear whether Abs blocking palm sweating and those acting at neuromuscular junctions have similar epitope recognition, class, isotype, and affinity. Although NST results vary and tests are not generally accepted, Kranz et al. ’s findings do not conflict with mouse protection assay (MPA) results, the gold standard for assaying blocking Abs.5 MPA typically employs five mice per test serum.4 If all mice survive the challenge with test serum LD100 of BoNT then serum has blocking Abs, which are absent if none survive. However, with some test sera not all mice die or conversely survive. If 4/5 to 1/5 mice survive, then the sample has blocking Abs, but at obviously decreasing titers. Operationally, 4/5, 3/5 mice surviving are considered MPA-positive and 2/5 or 1/5 are MPA-negative. Kranz et al.’s work might draw attention that MPA results, reported as MPA-positive or MPAnegative, should provide titer information (number of mice that die or survive). This could guide treatment and if blocking Abs start to appear, subsequent injection could be appropriately modified (e.g., increasing intertreatment interval).