Group A streptococcal (GAS) infection is associated with autoimmune disease, including Acute Rheumatic Fever (ARF). Sydenham’s chorea (SC) is the neurological manifestation of ARF occurring in up to 30% of patients and is characterised by random involuntary movements, irritability, attention deficit, and obsessive-compulsive disorder (OCD). Previous research has shown that a compromised blood brain barrier (BBB) is essential in allowing cross-reactive antibodies to enter the CNS. However, it is not yet known whether infection with GAS alone is enough to disrupt the BBB or if a secondary insult is needed to trigger disease. We hypothesised that a secondary insult is required for the development of neurological symptoms following a GAS infection.

In this study, Bordetella pertussis toxin (PT) was used as a secondary insult following immunisation with GAS recombinant M5 protein (rM5). The presence of antibodies against GAS rM5 was confirmed through an indirect ELISA. Neurobehavioral assessments showed significant abnormalities in fine motor control and the presence of OCD-like behaviour in rats immunised with GAS rM5 and administered PT but not GAS rM5 alone. Evaluation of BBB permeability, using Evans Blue Dye, confirmed that the BBB was only disrupted in rats injected with GAS rM5 and administered PT. We concluded that a secondary insult is required to disrupt the BBB and allow GAS rM5 antibodies to access the brain leading to the development of post-streptococcal neurological symptoms. Understanding the precise conditions and molecular basis under which SC develops will be critical to the development of future treatments of the disorder.