Infection and molecular mimicry in autoimmune diseases of childhood.

The etiopathogenesis of childhood chronic autoimmune disease is, in most cases, unknown. Most likely, several factors overlap in determining the loss of tolerance toward certain autoantigens that become the target of the disease and the main cause of its perpetuation. Infectious agents have often been implicated in the pathogenesis of these diseases, but, to date, compelling evidence for a horizontal transmission or for localized epidemics is lacking. Human pathogens may nevertheless play a role in determining the loss of tolerance toward certain self-antigens by means of mechanisms other than classic infection. It is common knowledge that human pathogens often express proteins with high antigenic potential with important homologies with human proteins. Evolutionary pressures based upon the necessity of escaping the host's specific immune responses may have determined this phenomenon, called "molecular mimicry". It is reasonable to assert that certain individuals can develop abnormal immune responses upon contact with an antigen that mimics a self-protein. These responses may ultimately lead to self-reactivity and autoimmune disease. In this model of molecular mimicry, self-reactivity is triggered by cross-recognition of a self and an exogenous protein that bear the same sequence. A disease triggered by such a mechanism should present with: i) some form of an acute or chronic autoimmune clinical manifestation; ii) a documented clinical correlation between contact with a human pathogen and the autoimmune disease; iii) immune cross-reaction between a protein from a pathogen and a homologous human protein. Acute rheumatic fever, Reiter's syndrome and the other reactive arthritides fulfill the above conditions.(ABSTRACT TRUNCATED AT 250 WORDS)