Autoimmunity can be considered as the presence of self-reactive adaptive immune components, and autoimmune diseases can be thought of as autoimmunity plus clinically apparent pathology 1, 2. Although proposals have been made regarding approaches to define autoimmunity and specific autoimmune diseases, there are still no commonly agreed-upon general criteria for these 3, 4. This lack of consensus in autoimmune disease definitions, and even agreement on which specific illnesses constitute the autoimmune diseases, impede research and clinical care, and the development of international stakeholder-defined consensus on these issues would greatly enhance further progress in the field.

The precise mechanisms for the development of autoimmunity and autoimmune diseases remain unclear, however, a growing consensus has developed that they evolve from still-to-be-defined gene-environment interactions 5, 6. As a result of technological advances made possible by the human genome project and related investigations, many genetic risk factors for autoimmune diseases have been identified [7], but there has been relatively little progress in deciphering the even more profound impact of environmental influences 8, 9. This is not surprising given the difficult tasks of assessing the doses, durations, and effects of the myriad combined environmental exposures we experience over a lifetime [10] and the complex impacts they have on the maturation and function of the immune system [11].

Studies have found increased frequencies of autoimmunity and autoimmune diseases over recent decades 12••, 13. Yet, there are many challenges in accurately assessing changes in the incidence and prevalence of autoimmunity and autoimmune diseases over time. First, as noted above, there is a lack of universal consensus on definitions of cases and disease criteria [3]. Second, many autoimmune disorders individually are rare and heterogeneous conditions that are likely underdiagnosed, with evidence of varying ethnic, racial, and geographic distributions, making current estimates of their actual numbers problematic 14, 15, 16. Third, there are inadequate centralized and standardized national and international databases on which to base these estimates, and there are referral biases to tertiary care centers from which much of our current information arises. Methodologies for autoantibody and other immune assays are constantly evolving, and each varies in accuracy, sensitivity, and specificity [17]. Finally, with increased understanding, classification and diagnostic criteria for some autoimmune diseases have evolved over time [18].