In the presence of a positive HEp-2 IFA screening test, is it always necessary to search for antibody specificity?

Yes, when possible, it is important to try and identify specific antibody targets.  There is a wide variety of known autoantibody targets in systemic rheumatic diseases and this is expanding at a rapid pace (7-9). The HEp-2 IFA screening test is able to reveal more than 100 different types of autoantibodies (1), only a portion of which have a validated clinical association and only about 30-40 of these can be revealed by routine laboratory assays. From a cost-benefit point of view, therefore, it is not possible to detect the target specificity in all positive ANA cases. There is international consensus that to bring clinical value to HEp-2 IFA it should be reflexed testing to a disease-specific solid-phase assay.