title: Microinfusion of antineuronal antibodies into rodent striatum: failure to differentiate between elevated and low titers.
abstract: An autoimmune-mediated mechanism has been proposed for several pediatric movement disorders. In a three-center (Brown, Yale, and Johns Hopkins) collaborative effort, serum antineuronal antibodies (ANAb) were measured by use of ELISA or immunohistochemical techniques on 35 children (mean age 11.4 years) with Tourette syndrome, attention deficit hyperactivity disorder, and/or obsessive compulsive disorder. Eight sera, 4 containing the highest and 4 the lowest levels of ANAb, were identified at each institution. Selected sera (total of 9 with elevated and 7 with low ANAb) were re-encoded and sent to each center for infusion into the ventrolateral striatum of 16 male Sprague-Dawley rats. Animals were observed for behavioral abnormalities for 3 days before the start of infusion, during infusion on days 2-4, and for 2 days after infusion. Combined stereotypy scores increased after antibody infusion, but there was no significant effect based on serum titer (p=0.85). Scores differed among centers, but analyses based on individual institutional data again failed to show an effect based on elevated or low ANAb values (Brown, p=0.95; Yale and Johns Hopkins, p=0.81). Post hoc studies with sham surgery and infusion of phosphate-buffered saline support suggestions of nonspecific behavioral effects unrelated to antibody titer. This report emphasizes that any conclusions about antibody-mediated movement disorders that are based upon results from the rodent infusion model must be considered with caution.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Jefferson Street Building 124, 600 N. Wolfe Street, Baltimore, MD 21287, USA. hsinger@jhmi.edu
authors.forename: Harvey S
authors.initials: HS
authors.lastname: Singer
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Mink
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Loiselle
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Burke
authors.forename: Irina
authors.initials: I
authors.lastname: Ruchkina
authors.forename: Syed
authors.initials: S
authors.lastname: Morshed
authors.forename: Salina
authors.initials: S
authors.lastname: Parveen
authors.forename: James F
authors.initials: JF
authors.lastname: Leckman
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Hallett
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lombroso
mesh_terms: D000293:Adolescent; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage / Q000096:biosynthesis* / Q000097:blood; D002648:Child; D003342:Corpus Striatum / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000502:physiology
chemical_list: D001323:Autoantibodies