Genetics of childhood disorders: XXXII. Autoimmune disorders, part 5: streptococcal infection and autoimmunity, an epidemiological perspective.

There is increasing recognition that microbial infections are important contributors to a wide range of chronic conditions. Peptic ulcer disease may be due to the bacterium Helicobacter pylori rather than to emotional stress and diet. For years the conventional wisdom had been that no microbe could survive the acidic conditions of the stomach. Until recently the blood-brain barrier was considered impenetrable to plasma proteins, such as antibody and complement. Now it is purported that several neuropsychiatric disorders of childhood are rooted in a microbetriggered autoimmune response. Clearly, a contributing role for microbial infections in chronic diseases of the CNS needs to be reassessed. Inflammation, sometimes accompanied by a specific immune response, is often a critical component of chronic diseases associated with infection. A role for microorganisms in autoimmunity has been suggested for decades, although for many diseases, such as multiple sclerosis and type I diabetes, the unequivocal identification of the etiological agent(s) has been met with difficulty. Perhaps the best-recognized link between autoimmunity and infection lies with acute rheumatic fever (ARF) and the bacterium Streptococcus pyogenes, also known as group A β-hemolytic streptococci (GABHS). Diagnosis of ARF can be tricky, and it generally includes one or more of the following major manifestations: (1) carditis, typically involving the mitral valve; (2) a polymigratory arthritis, which resolves without permanent damage to the joints; and (3) Sydenham chorea, a disorder of gross motor function. Essential to the diagnosis of ARF is evidence of a recent GABHS infection. Documentation can take the form of a positive throat culture or an elevated antibody titer to GABHS antigens. However, exceptions are made for some cases of “pure chorea.” Unlike carditis or polymigratory arthritis, there is the possibility of a delay of several months between the primary GABHS infection and the onset of Sydenham chorea symptoms. By this time, the organism is long gone from the host and anti-streptococcal antibody titers, as well as plasma markers for