Figure 2.

Factors that contribute to increased incidence and prevalence of autoimmunity in women. In women (46XX) with genetic susceptibility to autoimmune states, external environmental stimuli affect modifying factors as well as endocrine transitions via epigenetic mechanisms. Additionally, there are interactions between estrogens, androgens, leptin and prolactin on one hand and the interplay between Th1 and Th2 immune responses on the other. Both (endocrine and immune response) these phenomena are influenced in varying ways during the female transition states depending on the circulating concentrations of different hormones and immune cytokines, which in turn may be determined by epigenetics. Thus, hormonal fluctuation, immune polarization and transition states together drive susceptible women over the autoimmune “tipping point” leading to manifestation of overt clinical disease.