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Figure 1: Characteristics of tissue-specific and systemic autoimmune disorders. Tissue-specific autoimmunity originates in a specific tissue within an individual organ usually initiated by a single autoantigen. Dendritic cell MHC presentation of this antigen to cognate autoreactive T cells amplifies an adaptive immune response that kills the antigen producing cells. The death of these cells releases a variety of cellular antigens that amplify the inflammatory immune response (antigen spreading), represented here as stars. In contrast, systemic autoimmunity autoantigens may originate independently within different tissues or organs in the body, for example, connective tissues in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Thus, antigen spreading can originate from multiple tissues in a variety of affected organs at different times (multiple stars), leading to diverse inflammatory disease progression from patient to patient. Several tissue-specific autoimmune diseases and their organs of origin are listed (left). Autoimmune diseases originating in several organs (center) and systemic autoimmune diseases originating independently in many organs throughout the body are indicated (right).