Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection

Abstract

The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fisher's exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection.

Antineural antibody in patients with Tourette’s syndrome and their family members

“…Most studies involving antineuronal antibodies have been in those patients with tics with Streptococcus-related symptoms. There were very few studies which have considered antineuronal antibodies in patients with Tourette's syndrome, the clinical symptoms of which do not correlate with streptococcal infection.The most recent study compared the PANDA group and the uncomplicated active Group A streptococcal infection children and found that the presence of antibrain antibody could not be explained merely by the history of GABHS infection [32]. The sera from clinical OCD cases showed antibodies directed against caudate and putamen at a rate significantly higher than that of clinical controls, providing evidence of basal ganglia involvement in OCS without Streptococcus infection [4].…”

“…The striata were carefully dissected out under a dissecting microscope, according to the procedures described by Smart and Sturrock [32,35]. They were then placed into another dish containing ice-cold phosphate-buffered saline (PBS) to thoroughly remove blood vessels and membranes from the striatal tissues.…”

“…In the past, research has focused on the manner of inheritance, or the genetic linkage, with very few contributions coming from association studies. There is growing evidence that both autoimmune and genetic factors are involved in the pathogenesis of TS [28][29][30][31][32] although a study tried but failed to identify such a marker by investigating choline in the red blood cells of TS twins and their parents [33]. Therefore, it is considered a trait marker that is indicative of a genetic susceptibility to Tourette's syndrome [33,34].…”

The Immunobiology of Tourette's Disorder, Pediatric Autoimmune Neuropsychiatric Disorders Associated withStreptococcus, and Related Disorders: A Way Forward

“…Potential mechanisms by which these autoantibodies cause clinical manifestations in central nervous system (CNS) diseases include direct stimulation or blockade of receptors in the basal ganglia, or immune complexes promoting inflammation of these brain regions (Giedd et al 1996(Giedd et al , 2000. Antineuronal antibody binding to basal ganglia tissue was found in both patients with PANDAS (Pavone et al 2004) and patients with ADHD (Sanchez-Carpintero et al 2009), whereas in SC patients, increased antineuronal antibody binding to basal ganglia tissue correlates with symptom severity (Church et al 2002;Husby et al 1976;Kotby et al 1998). More recently, monoclonal antibodies to N-acetyl-beta-d-glucosamine, the dominant epitope of GAS carbohydrate, and lysoganglioside GM1, a neuronal cell-surface molecule, have been cloned from children with SC (Kirvan et al 2003(Kirvan et al , 2006.…”

PANDAS: current status and directions for research

“…Investigators are now finding antineuronal antibodies among the PANDAS subgroup that are specific to the basal ganglia as well. 75,76 Preliminary results suggest that an antineuronal antibody found in SC patients that stimulates neuronal transduction may also be present in a group of PANDAS subjects (Kirvan, 2003 personal communication).…”