Although most of these assays can accurately measure ANA (104), problems with the standardization and calibration become more and more evident. The comparability between laboratories is very poor even when the same technology is used (33). These differences most likely result from variable detection of ANA, depending on their-fine specificity and ability to bind to native, as opposed to denatured, antigenic determinants: detergent solubilized proteins are denatured and therefore may not bind antibodies specific for discontinuous or conformational determinants that require an intact protein. In addition, some antigenic determinants may be influenced by their association with other proteins or RNA and disappear when highly purified or dissociated
The currently available international or national reference preparations for many antibody specificities are not sufficient for an effective standardization (105). The use of so-called ANA consensus sera - now available for use in the detection of SS-A, SS-B, Sm, U1-RNP, Scl-70, Jo-1, dsDNA, and centromere antibodies - should only serve as interim solution (106). Quality assurance schemes reveal large differences reported by different assays for some analytes, even when calibrated against an international or an equivalent reference preparation. Serial results can therefore only be compared from the same laboratory. At present it is very important that the laboratorians become familiar with the limitations of the technology currently in use, and to consult with the clinicians in cases of doubt.