An autoimmune response to streptococcal antigens is believed to produce rheumatic fever (RF), including one of its major manifestations, Sydenham's chorea (SC). An interplay of genetic, developmental, and environmental factors determines vulnerability to these complications of strep infection. Swedo et al, have hypothesized that SC may be a medical model for some forms of tic and obsessive compulsive disorders (OCD). We sought a marker that could identify which and how many cases of OCD or Tourette's Syndrome (TS) might have an illness that bears a pathobiologic relationship of SC. Monoclonal antibody (mAb) D8/17 identifies a B cell antigen with expanded expression in all patients with RF, 15percent of unaffected relatives of patients with RF, and in about 5 of controls. It is thought to be a trait marker for susceptibility to RF. In our pilot study, 31 clinic patients ages 7-24 years with childhood-onset OCD and/or TS participated. None carried the diagnosis of RF or SC. D8/17 was positive in all patients whereas only 1 of 21 healthy control was positive. These findings suggest that D8/17 may serve as a marker for shared susceptibility amongst childhood-onset OCD, TS, and SC. The proposed study will address the following questions: 1) Is D8/17 positivity specific to childhood-onset OCD/TS? The frequency of D8/17 positivity in a cohort of 45 patients with childhood onset OCD/TS will be compared with 30 patients with adult onset OCD and 30 ages/sex-matched healthy controls. We hypothesize that D8/17 levels will be highest in the childhood-onset group, intermediate in the adult-onset group, and lowest in the healthy controls. 2) What is the relationship of D8/17 expression to clinical state? Forty D8/17 positive children with OCD/TS will be followed for clinical status, D8/17 expression, and evidence of streptococcal infection at 3-month intervals. 3) Is D8/17 positivity familial in childhood onset OCD/TS? Structured psychiatric interviews and D8/17 expression will be determined in all available biological first degree relatives of 40 probands with childhood onset OCD/TS and of 30 healthy controls. 4) Is D8/17 positivity a peripheral marker for risk of developing OCD/TS? Forty-eight unaffected (i.e., no evidence of OC/tic symptoms or RF) but D8/17 positive """"""""at-risk"""""""" children and 48 controls (unaffected D8/17 negative children) will be followed prospectively for development of symptoms of OCD or TS as well as acute RF at 6-month intervals
| Murphy, T K; Benson, N; Zaytoun, A et al. (2001) Progress toward analysis of D8/17 binding to B cells in children with obsessive compulsive disorder and/or chronic tic disorder. J Neuroimmunol 120:146-51 |
| Murphy, T K; Goodman, W K; Ayoub, E M et al. (2000) On defining Sydenham's chorea: where do we draw the line? Biol Psychiatry 47:851-7 |
