title: Antineuronal antibodies in a heterogeneous group of youth and young adults with tics and obsessive-compulsive disorder.
abstract: OBJECTIVE
  Antineuronal antibodies have been implicated in tic and obsessive compulsive disorders (OCD) associated with group A streptococcal infections. We investigated antineuronal autoantibody levels as well as antibody-mediated neuronal cell signaling activity, as previously reported for Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS), to determine immunological profiles for a large cohort of children with tics and/or OCD.
  
  
  METHODS
  Study participants (n=311; ages 4-27 years, 66% male) were selected from a larger group of individuals with self-reported neuropsychiatric symptoms (n=742) and included only those with accurate knowledge of group A streptococcal infection status, except for four individuals in whom streptococcal infection status was unknown. Healthy control samples (n=16; ages 5-14 years, 81% male), came from the National Institute of Mental Health and Yale University. In addition to serum donations, participants and/or legal guardians provided neuropsychiatric and related medical histories of symptoms that had lasted >1 year. Antineuronal immunoglobulin G (IgG) titers were measured by standard enzyme-linked immunosorbent assay (ELISA) and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was tested in serum.
  
  
  RESULTS
  Of 311 individuals, 222 (71%) had evidence of group A streptococcal infection, which was associated with tics and/or OCD status (p=0.0087). Sera from individuals with tics and/or OCD (n=261) had evidence of elevated serum IgG antibodies against human D1R (p<0.0001) and lysoganglioside (p=0.0001), and higher serum activation of CaMKII activity (p<0.0001) in a human neuronal cell line compared with healthy controls (n=16). Furthermore, patients with tics and OCD had significantly increased activation of CaMKII activity compared with patients with only tics or only OCD (p<0.033 for each).
  
  
  CONCLUSIONS
  Our study suggested a significant correlation of streptococcal-associated tics and OCD with elevated anti-D1R and antilysoganglioside antineuronal antibodies in serum concomitant with higher activation of CaMKII in human neuronal cells. Youth and young adults with chronic tics and OCD may have underlying infectious/immunologic etiology.
authors: 1 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma.
authors: Carol J
authors: CJ
authors: Cox
authors: Amir J
authors: AJ
authors: Zuccolo
authors: Erica V
authors: EV
authors: Edwards
authors: Adita
authors: A
authors: Mascaro-Blanco
authors: Kathy
authors: K
authors: Alvarez
authors: Julie
authors: J
authors: Stoner
authors: Kiki
authors: K
authors: Chang
authors: Madeleine W
authors: MW
authors: Cunningham
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D009474:Neurons; D009771:Obsessive-Compulsive Disorder / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D013290:Streptococcal Infections / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D020323:Tics / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D055815:Young Adult
chemical_list: D001323:Autoantibodies