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Comparative Study
, 8 (9), e73516
eCollection

Dopamine Receptor Autoantibodies Correlate With Symptoms in Sydenham's Chorea

Affiliations
Comparative Study

Dopamine Receptor Autoantibodies Correlate With Symptoms in Sydenham's Chorea

Hilla Ben-Pazi et al. PLoS One.

Abstract

Background: Sydenham chorea (SC), a neuropsychiatric sequela of group-A streptococcal infection, is associated with basal ganglia autoantibodies. Although autoantibodies have been proposed in neuropsychiatric disorders, little evidence has been shown to link autoimmunity and clinical symptoms. We hypothesized that dopamine receptor-autoantibody interactions may be the basis of neuropsychiatric symptoms in SC.

Methods: Sera from 22 children with SC (age 10.7±4.5 years) and 22 age-matched controls were studied. Clinical neuropsychiatric symptoms were measured in SC at sample collection using the UFMG-Sydenham's-Chorea-Rating-Scale (USCRS). Anti-dopamine D1 receptor (D1R) and anti-dopamine D2 receptor (D2R) autoantibodies were measured by the enzyme linked immunosorbent assay (ELISA) and were correlated with clinical symptoms.

Results: Anti-D1R and anti-D2R autoantibodies were significantly higher in SC compared to controls (n = 44; p = 0.010 and p = 0.017, respectively). We found that the ratio (anti-D2R/D1R) of the two anti-dopaminergic receptor antibodies correlated with neuropsychiatric symptoms as determined by USCRS measurements (n = 18; r = 0.53, p = 0.024). In addition, anti-D2R titers correlated with antistreptolysin-O titers (n = 43; r = 0.49, p = 0.0008).

Interpretation: Our report linked, for the first time, autoimmunity with neuropsychiatric symptoms. The significant correlation was found using ratios of autoantibodies against dopamine receptors (anti-D2R/D1R) rather than the absolute elevated individual anti-D1R or anti-D2R titers. We suggest that autoantibodies may lead to a receptor imbalance and induce greater sensitivity to dopamine signaling potentially leading to neuropsychiatric symptoms in SC. Our novel findings suggesting altered balance in the dopaminergic system may provide a new approach in understanding autoimmune neuropsychiatric disorders with possible implications for diagnosis and treatment.

Conflict of interest statement

Competing Interests: Dr. Ben-Pazi and Prof. Stoner declare that no competing interests exist. Prof. Madeleine Cunningham declares a conflict of interest as Chief Scientific Officer of Moleculera Labs, which is a start up company offering a panel of diagnostic immunological tests for diseases such as Sydenham chorea (SC) and Pediatric Acute Onset Neuropsychiatric Syndrome (PANS). Prof. Cunningham has filed for a provisional patent on her panel of assays with algorithm to detect autoantibodies against the brain in childhood diseases such as SC and PANS. Details are: provisional patent application for anti-neuronal antibody algorithm for autoantibodies in neuropsychiatric disorders with an application number of 61787919 filed on March 15, 2013. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Distribution of Anti-D1R and Anti-D2R IgG antibody titers of Sydenham's chorea patients and controls.
Box plots present Sydenham's chorea (SC; grey) and control (white) group anti-D1R and anti-D2R titers between 25th and 75th percentiles with elevated mean (triangle) and median (bar) titers in SC. Median and percentiles may share same values due to multiple measurements.
Figure 2
Figure 2. Dopamine receptor antibody ratio (D2R/D1R) correlates with neuropsychiatric symptoms (USCRS score).
Autoantibody ratio against dopaminergic receptors correlated with the clinical motor and non-motor symptoms. Total USCRS ratings (n = 18, mean 19.1±11.9) correlated with anti-D2R/anti-D1R ratio (r = 0.53, P = 0.024) suggesting that the receptor imbalance may lead to dopaminergic hypersensitivity causing the clinical neuropsychiatric symptoms.
Figure 3
Figure 3. Motor scores correlate with non-motor scores of SC patients evaluated by USCRS.
USCRS rates motor and non-motor symptoms on a 0–4 severity scale (0 = none to 4 =  severe). In our patients the sum of motor symptom (items 7–21) were closely correlated (r = 0.70, P = 0.0011) with the sum of non-motor items (1–6).

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