Annotation: PANDAS: a model for human autoimmune disease

Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS) is a recently recognized syndrome in which pre-adolescent children have abrupt onsets of tics and/or obsessive-compulsive symptoms, a recurring and remitting course of illness temporally related to streptococcal infections, and associated neurologic findings including adventitious movements, hyperactivity and emotional lability. Methods: Inspired by observations of similar symptoms in children with Sydenham’s chorea, a search was undertaken for clinical and laboratory evidence in support of the new syndrome. Results: Consistent and predictable clinical findings have been described in a large case series. Magnetic resonance imaging has supported the postulated pathobiology of the syndrome with evidence of inflammatory changes in basal ganglia. Antibasal ganglia antibodies have been found in some acute cases, mimicking streptococcal antigen epitopes. Conclusions: While PANDAS remains a controversial diagnostic concept, it has stimulated new research endeavors into the possible links between bacterial pathogens, autoimmune reactions, and neuropsychiatric symptoms. Keywords: PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections, Sydenham’s chorea, streptococcal infection, autoimmunity, tics. Abbreviations: SC: Sydenham’s chorea; EAE: experimental allergic encephalomyelitis; ARF: acute rheumatic fever; GAS: group-A beta-hemolytic streptococcus pyogenes; OCD: obsessive-compulsive disorder; ASO: antistreptolysin O; TS: Tourette’s syndrome; ADHD: Attention-Deficit/Hyperactivity Disorder; IVIG: intravenous immunoglobulin. Human beings have evolved in an environment sometimes threatening to their survival. Animals, bacteria, fungi, protozoa, viruses, and some as yet incompletely characterized ‘life’ forms (e.g., prions) have at times all attached themselves to human hosts and caused disease. Most of these until recently were, because unseen, largely unsuspected. That humanity survives is evidence of the effectiveness of its defenses. But the pathogens evolve as well, sometimes exploiting weaknesses in human immune systems. One of their techniques is mimicry of the molecular antigen epitopes that are recognized by human hosts as self (Cunningham & Fujinami, 2000). It is postulated that by making use of molecular mimicry, pathogens can evade host immune defenses which are designed to distinguish between host and foreign antigens. The mimicry is not complete, so the host’s immune system still mounts a defense against the invading organism. In the process, the ‘look-alike’ antigens provoke a loss of selftolerance. The outcome may be autoimmune disease, in which the host immune system is now directed at self-antigen, resulting in damage to the tissues that display the antigen. This annotation will review the evidence for autoimmune disorders, in the central nervous system in particular. It will review the contemporary evidence for the autoimmune etiology of Sydenham’s chorea (SC), a disorder first described in the seventeenth century. And it will outline the clinical and laboratory support for a newly recognized autoimmune