Mechanisms for induction of autoimmunity in humans

The triggering or immunogenic stimulus for human autoimmune diseases is unknown. It is not even known whether the stimulus is endogenous, i.e. truly "self" or exogenous, "non-self". Many autoimmune diseases are human lymphocyte antigen (HLA)-associated and demonstrate linkage to the HLA chromosome in family investigations. For most of these diseases, evidence is strong that the association is directly dependent on specific HLA class I or II molecules rather than on other genes located in the HLA region. Since HLA polymorphic HLA molecules have so far only been shown to have two distinct functions, both of which are immunological, a HLA association supports the notion that a particular disease is autoimmune. Furthermore, an association to a specific HLA allele implies that the immunogenic stimulus for autoimmunity would be one specific HLA-binding peptide and that, at least initially, autoimmunity is dependent on the reactivity of one or a limited number of potentially autoaggressive T cell clones. These findings are encouraging and formin the basis for future preventive measures. One current theory is that autoimmune disease is precipitated by an environmental agent, such as a viral infection. Several different mechanisms to explain how a viral infection could induce autoimmune disease in humans are described and one specific example is presented for a virus-induced autoimmune disease in humans. The question of whether ITP could also be dependent on such a mechanism is briefly discussed.