Long-term variability in immunofluorescence titer of antibodies to nuclear antigens observed in clinical laboratory proficiency testing surveys

Context.-Presence of antibodies to nuclear antigens (ANAs) above a threshold titer is an important diagnostic feature of several autoimmune diseases, yet titers reported vary between laboratories. Proficiency survey results can help clarify factors contributing to the variability. Objective.-To determine the contribution of HEp-2 ANA kits from different manufacturers to the variation in titers, and assess whether the differences between kits are consistent over the long term. Design.-HEp-2 ANA titers reported by laboratories participating in the external quality assessment proficiency testing surveys conducted by the College of American Pathologists between 2008 and 2018 were analyzed. The ANA titers reported for each specimen were ranked according to the kits being used by testing laboratories, and the statistical significance of the differences was determined. Results.-The ANA titer results were strongly influenced by the HEp-2 ANA kit used (P,.001). During the 11 years studied, the rank order of the ANA titer for each kit relative to the other kits was remarkably consistent. The rank of ANA titer for individual ANA patterns observed for each kit was similar to the overall rank of that kit. Conclusions.-Variability in ANA titers was strongly associated with the kits used, and the differences between kits were quite consistent during the 11 years studied. Because the variability is not random, it has the potential to be managed by harmonizing kits, which could lead to improved consistency in reporting ANA titers.