An understanding of the prevalence and titers of ANAs in various subsets of the population of normal individuals, and of the effects that different technical factors may have on measurement of these antibodies, is important to the interpretation of ANA results from study populations of symptomatic and asymptomatic women with silicone breast implants. The type of tissue that is used as the substrate (antigen) in the performance of the ANA test can affect the frequency of positive tests at all titers. In the mid-1980s and early 1990s, laboratories used frozen sections of mouse or rat liver as the test substrate. More recently, human tissue culture cells, such as HEp-2 cells, have replaced animal liver (or kidney) sections. Prevalence and titers of ANAs are higher when tissue culture cells, rather than mouse liver, are used as a substrate (Fritzler et al., 1985; McCarty et al., 1984). Hollingsworth et al. (1996) reported results of comparative ANA testing of 106 healthy females and 91 healthy males. There were more positive tests at all titers when HEp-2 cells were used than when rat liver was used. Also, the prevalence was nearly twice as high in normal women as in men (Hollingsworth et al., 1996). Measurements in controls using mouse or rat liver (or other tissues) cannot be compared to values from women with breast implants using human tissue culture cells.
There are differing views on what titer and what intensity of fluorescence constitute a positive ANA test. Reports of ANA prevalence in women with breast implants have not always used the same criteria to define positivity. Furthermore, differences in the performance of the ANA test and in the results obtained are common across different laboratories. These factors make it essential that studies use the same laboratory at the same time for ANA assays of experimental and control women. Strongly positive ANA tests in women with implants who have connective tissue disease undoubtedly reflect the disease. These positive ANA tests should not be ascribed to the presence of the implants. Moreover, studies from investigators with a special interest in autoantibodies or a particular connective tissue disease may have attracted a nonrepresentative group of women with implants and with connective tissue disease.
In 1997, an important analysis of ANAs in normal sera was carried out by a subcommittee of the International Union of Immunological Societies' Standardization Committee (Tan et al., 1997). The objective of this study, carried out in 15 laboratories from around the world, was specifi-