CNS autoimmune disease after Streptococcus pyogenes infections: animal models, cellular mechanisms and genetic factors

Future Neurol. 2016 Dec;11(1):63-76. doi: 10.2217/fnl.16.4.


Streptococcus pyogenes infections have been associated with two autoimmune diseases of the CNS: Sydenham's chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). Despite the high frequency of pharyngeal streptococcus infections among children, only a small fraction develops SC or PANDAS. This suggests that several factors in combination are necessary to trigger autoimmune complications: specific S. pyogenes strains that induce a strong immune response toward the host nervous system; genetic susceptibility that predispose children toward an autoimmune response involving movement or tic symptoms; and multiple infections of the throat or tonsils that lead to a robust Th17 cellular and humoral immune response when untreated. In this review, we summarize the evidence for each factor and propose that all must be met for the requisite neurovascular pathology and behavioral deficits found in SC/PANDAS.

Keywords: PANDAS; Streptococcus pyogenes; Sydenham’s chorea; Th17 cell; autoantibodies; autoimmunity; blood–brain barrier; gene set analysis; major histocompatibility complex; pathway-based genomic studies.