Intracellular autoantigens: diagnostic fingerprints but aetiological dilemmas

Autoimmune diseases such as systemic lupus erythematosus, scleroderma, Sjögren's syndrome, mixed connective tissue disease and dermato/polymyositis are each characterized by distinct sets of autoantigens and antibodies which confer on each disease a specific immune profile or fingerprint. These immune fingerprints have advanced our management of this group of diseases, as aids in differential diagnosis and earlier recognition. In lupus and scleroderma, multiple antigen/antibody systems characterize these fingerprints and the autoantigens appear to be located in separate cell compartments of the nucleus, nucleolus and cytoplasm. Because these antibodies are so distinctive for each disease, the response must be antigen driven or at least antigen directed. However, the apparent multi-focus location of the autoantigens poses a problem. It now appears that in scleroderma this dilemma may be explained by the consideration that at a certain time point in cell metabolism all the known autoantigens may be assembled at one location to form a single structural entity. It is possible that this assembly of antigens may be required for a specific cellular function. An autoimmune response to this transiently assembled structure comprising several different proteins and nucleic acids could result in the complex immune response seen in this disease.