{'fraction_non_alphanumeric': 0.025210084033613446, 'fraction_numerical': 0.011428571428571429, 'mean_word_length': 5.5550660792951545, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Reopening the case for anti–basal ganglia antibodies (ABGAs): Identification of dopamine‐2 receptor antibodies associated with movement disorders

The story of anti–basal ganglia antibodies (ABGAs) began in 2002, when Church et al. described them in Sydenham’s chorea, a movement disorder suggestive of autoimmune origin. Following that, the concept of autoimmune basal ganglia disorders received much interest and consequently ABGAs were said to be associated with a variety of neuropsychiatric and movement disorder conditions, ranging from pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), Tourette’s syndrome, dystonia, parkinsonism, and also encephalitis lethargica. However, the pathogenic relevance of ABGAs was questioned as they were detected using soluble brain extract, a method unlikely to identify antibodies targeting membrane proteins but rather an intracellular antigen. This stands in stark contrast to the new paradigm in neuroimmunology, namely that antibodies of pathological significance must bind to antigens on the cell surface which are involved in neurotransmission; e.g., receptors, ion channels, or associated proteins. Now, a new publication by Dale et al. renews this debate. Hypothesizing that patients with autoimmune basal ganglia disorder harbor antibodies against surface proteins of dopaminergic neurons, they used a flow cytometry cellbased assay to identify elevated levels of immunoglobulin G (IgG) against the dopamine 2 receptor (D2R) in 12 of 17 children with encephalitis with movement disorder compared to 0 of 67 controls. Sera positive for D2R-IgG labeled MAP2 positive striatal neurons in wild-type mouse brain. The labeling was decreased in D2R knockout striatum or after immunoadsorption of sera with D2R expressing human embryonic kidney cells. No antibodies directed against other dopamine receptor types (D1R, D3R, D5R) were found. In a second step, they detected D2R-IgG in 10 of 30 patients with Sydenham’s chorea, 0 of 22 with PANDAS, and 4 of 44 with Tourette’s. The authors conclude that D2R antibodies can account for movement and psychiatric disorders of autoimmune origin and propose D2R might be a diagnostic biomarker. This study is well-thought-out and elegantly performed, yet there are some caveats. Again, the presence of autoantibodies in the serum does not necessarily mean that they are pathogenic. For example, multiplicity of antibodies is not uncommon in autoimmune disorders, and also occurrence of antibodies as an epiphenomenon, possibly due to ongoing tissue destruction, seems conceivable. These findings need to be replicated independently to determine their significance, and as for other autoantibodymediated diseases, it would be interesting to investigate the mechanisms of action on neurophysiological basis and in transfer experiments. Thus we have a new chapter in the basal ganglia antibodies story and it appears that it is to be continued.