TO THE EDITOR: Susan E. Swedo, M.D., and colleagues recently reported that a trait marker for rheumatic fever (D8/17) could identify children with pediatric autoimmune neuropsychiatric disorders (obsessive-compulsive disorder [OCD] and tic disorders) associated with streptococcal infections (PANDAS) and Sydenham's chorea (1). Eighty-five percent of children with PANDAS, 89% of children with Sydenham's chorea, and only 17% of healthy comparison subjects were D8/17 positive (≥12% D8/17+ cells).

This is an important finding that has potentially far-reaching consequences with respect to identification of subtypes of OCD (2), understanding the relationship between Sydenham's chorea and OCD (3), defining the role of poststreptococcal autoimmune factors in OCD (4), and developing new therapeutic strategies for these disorders (2). However, alternative theoretical perspectives and additional methodological descriptions may be helpful in gauging the full impact of these important findings.

The childhood-onset variants of obsessive-compulsive and tic disorders are known to have a marked male predominance (5). Thus, gender may conceivably be a factor in the expression of D8/17 positivity. Since the groups appear to differ by sex, with more male subjects in the PANDAS group (70.4%, N=19 of 27) than in the healthy comparison group (29.2%, N=7 of 24) (χ²=8.63, df=1, p=0.003), exploration of an overall sex effect on D8/17 positivity would be of interest. Likewise, mention of the prevalence of antistreptococcal antibodies (i.e., anti-streptolysin O and anti-DNase B) in the groups would be helpful in determining the relative rates of recent streptococcal infection in each of the groups.

It is unknown whether D8/17 positivity is specific for PANDAS, Sydenham's chorea, and rheumatic fever or if it also occurs in other neuropsychiatric disorders. Studies of psychiatric disorders without poststreptococcal symptom exacerbation would help clarify whether D8/17 either is involved in an autoimmune response or serves as a genetic marker for select neuropsychiatric disorders. If D8/17 level were found to be correlated with repetitive behaviors as measured by Yale-Brown Obsessive Compulsive Scale severity, this might support a dimensional approach to D8/17 mediation of compulsive symptoms across traditional diagnostic boundaries.