Infusion of Sydenham's chorea antibodies in striatum with up-regulated dopaminergic receptors: a pilot study to investigate the potential of SC antibodies to increase dopaminergic activity.

BACKGROUND: Sydenham's chorea (SC) is a neurological manifestation of rheumatic fever. Autoimmune mechanism of SC is supported by clinical improvement with immunomodulatory therapy; presence of circulating serum anti-basal ganglia antibodies; increase in Th2 group of cytokines in serum and CSF of patients. However, a role of the antibodies in the pathogenesis can only be established by their passive transfer. Chorea is a manifestation clearly related to increased dopaminergic (DA) activity. The purpose of this study was to investigate the potential of antibodies from patients with Sydenham's chorea to cause behavior alterations on rats with unilateral post-synaptic dopamine receptor up-regulation. METHODS: Rats previously submitted to 6-hydroxidopamine (6-OH-DA) unilateral lesion of substantia nigra pars compacta (SNc) and tested with apomorphine to ensure DA receptors up regulation, received intrastriatal infusion of antibodies from SC patients (n=4) or healthy controls (n=3) during 48 h. 24h post infusion initiation (24PI) and 48 h post infusion initiation (48PI), we registered the occurrence of spontaneous contra lateral rotations (CLR). FINDINGS: SC group exhibited significantly higher number of CLR than control group at 24PI (p=0.049) and 48PI (p=0.048). CONCLUSION: The limited sample of the present study restricts us to affirm that SC is really an immune-mediated condition. However the significant result of this pilot study points to preliminary evidence that SC antibodies may affect DA activity in rats with up-regulated striatal DA receptors.

Monocyte dysfunction in Sydenham's chorea patients.

Until now, there are no conclusive data about the mechanisms involved in motor symptoms of Sydenham's chorea (SC). Taking into account the autoreactive antibody-mediated hypothesis of SC pathogenesis, the SC may be associated with uncontrolled immune mechanisms. Besides the antibody hypothesis, the innate immune system has been underappreciated. Hence, we evaluated the activation state of monocytes, cells that are precursors of macrophages, to characterize the inflammation profile of patients. We assessed the surface molecules CD80, CD86, and human leukocyte antigen DR expression in patients with SC by flow cytometry analysis. Our results showed a decreased CD14(+) (monocyte) frequency, with concomitant increased CD14(-) frequency inside monocyte population. Although monocyte population showed a decreased human leukocyte antigen DR and CD86 frequencies, the CD14(-) population showed an increased frequency of CD80(+) monocyte from SC compared with controls. These data suggest that monocytes showed a reduced costimulatory potential in SC.

Serum levels of brain-derived neurotrophic factor in Sydenham's chorea.

Sydenham's chorea (SC) is the neurologic manifestation of rheumatic fever. In addition to involuntary movements, SC patients show behavioral changes, such as hyperactivity, obsessions, and compulsions. Brain-derived neurotrophic factor (BDNF) is related to neuronal development and differentiation. Since BDNF serum levels are altered in a series of neuropsychiatric disorders, such as schizophrenia and Huntington's disease, we investigated the serum levels of BDNF in SC patients. Eighteen patients with acute SC, 4 with persistent SC and 27 control subjects were included in this study. BDNF was determined by ELISA. There was no significant difference between BDNF serum levels of control and acute SC groups (P = 0.12). Persistent SC patients presented decreased BDNF levels when compared to both control and acute SC groups (P < 0.001). Our results suggest that the persistence of symptoms in SC may be related to structural changes in the central nervous system as expressed by altered BDNF levels.

Serum from Sydenham's chorea patients modifies intracellular calcium levels in PC12 cells by a complement-independent mechanism.

The proposed pathogenesis of Sydenham's chorea (SC) is an autoantibody-mediated basal ganglia dysfunction. Our study has shown that incubation of PC12 cells with complement-inactivated serum from SC patients was associated with a significant increase in Ca2+ levels evoked by KCl stimulus (mean +/- SEM, 341.0 +/- 8.7% of fluorescence intensity, arbitrary units) when compared with incubation with control serum (313.8 +/- 8.7% of fluorescence intensity, arbitrary units; P = 0.01). The increase in Ca2+ levels determined by SC patients sera correlated directly with the enzyme-linked immunosorbent assay optical density values for anti-basal ganglia antibodies. Our study supports the hypothesis that antibodies against basal ganglia in SC may cause their dysfunction.

Increased serum concentrations of monokine induced by interferon-gamma/CXCL9 and interferon-gamma-inducible protein 10/CXCL-10 in Sydenham's chorea patients.

Sydenham's chorea (SC) is thought to result from the action of streptococcus-induced antibodies that cross react with basal ganglia antigens. Much less is known, however, about the involvement of cellular mechanisms in its pathogenesis. Since chemokines seem to play a role in several CNS inflammatory disorders, we sought to investigate the chemokine profile of patients with SC. Increased serum levels of CXCL9, formerly monokine induced by interferon-gamma (Mig), and CXCL10, formerly interferon-gamma-inducible protein of 10 kDa (IP-10) were demonstrated in acute SC patients, suggesting that a particular group of chemokines may be involved in SC pathogenesis.

Detection of haemoglobin D Punjab in patient with Sydenham's chorea.

In the present report the authors identified a rare haemoglobin, Hb D Punjab, in association with Sydenham's Chorea. They emphasize the importance of characterizing unusual haemoglobins by peptide mapping, particularly when the electrophoretic pattern shows the characteristics of known haemoglobins and when associated with pathologic states.