Overview: infectious agents as etiologic triggers of autoimmune disease.

Abstract

Infectious agents, particularly viruses, are implicated in autoimmunity on the basis of three findings. First, autoimmune responses are made de novo or those already present are enhanced concomitant with infection by a wide variety of human DNA and RNA viruses. This point is strengthened by the second finding that, in experimental animals, both acute and persistent virus infections can induce, accelerate, or enhance autoimmune responses and cause autoimmune disease. For example, it has been shown that with the New Zealand mouse family, a genetically defined group of mice from which certain strains spontaneously develop autoimmunity, autoimmune manifestations normally present in NZB mice (DNA-specific antibodies, red blood cell-specific antibodies) or their (NZB × W) F1 relatives (DNA-specific antibodies) are enormously enhanced by persistent infection with either a DNA (polyoma) or RNA (lymphocytic choriomeningitis, LCMV) virus; that is, antibodies form earlier and reach higher titers in the infected mice than in their uninfected counterparts (Tonietti et al. 1970; Lampert and Oldstone 1973). Further, NZW mice, which normally do not develop these autoimmune responses, do so upon polyoma or LCMV infections. Indeed, the responses in NZB, (NZB × W) F1, or NZW mice are so marked that autoimmune diseases occur at a higher incidence with earlier time of death (NZB, (NZB × W)F1] or appear de novo (NZW). These events were subsequently repeated with a number of viruses, including retroviruses (reviewed Oldstone 1972). Third, utilizing an investigative approach that focuses on one potential mechanism where by microbes cause autoimmunity, molecular mimicry, a number of etiologic agents have been defined as potential causes of autoimmune disease (Oldstone 1987).