Harmonization of antineutrophil cytoplasmic antibodies (ANCA) testing by reporting test result-specific likelihood ratios: position paper

Abstract

To the Editor, Antineutrophil cytoplasmic antibodies (ANCA) are valuable laboratory markers to support the diagnosis of ANCAassociated vasculitis (AAV). High-quality immunoassays for proteinase-3 (PR3)-ANCA and myeloperoxidase (MPO)-

ANCA Testing in Clinical Practice: From Implementation to Quality Control and Harmonization

“…With respect to harmonization, the multicenter study that was the basis of the revised consensus, interestingly, revealed that if results were reported in terms of likelihood ratios for test result intervals that were defined by pre-set levels of specificity, the likelihood ratios were very similar for the different assays included in the study (18). The level of harmonization that can be achieved by this approach is very promising and even resulted in a position paper, signed by relevant stakeholders in ANCA testing, that proposes to employ test result-specific likelihood ratios to align test result interpretation across assays and manufacturers and to convey clinical information intrinsic to the antibody level (19). Reporting test results as likelihood ratio will greatly facilitate interpretation of the results in the context of the clinical presentations of the patients, since there is a clear relationship, as defined by the Bayes theorem, between pre-test probability, likelihood ratio and post-test probability (47).…”

“…As such, it is most appropriate to use quantitative assays, while keeping in mind that the assays are primarily designed for diagnostic purposes. For diagnosis quantitative ANCA results are important because higher ANCA levels are associated with higher likelihood ratios and, therefore, with increased certainty of the right diagnosis (18,19). For follow-up it is important to monitor possible decreases in ANCA levels upon therapy, but also to monitor possible increases as potential predictor for an upcoming relapse (10,11).…”

Likelihood Ratio Approach and Clinical Interpretation of Laboratory Tests

“…Another advantage of using LRs is the harmonization of different techniques, scales, units etc. (24). It certainly would make it easier for the clinician to interpret one single scale, namely LR, than having to get acquainted with different titers, units/ml, ug/ml, mmol/l etc.…”

“…But often, especially in non-harmonized test systems and when the result is at a level near the cut-off point between positivity and negativity, the information content of the result will be overestimated and therefore misleading. As an example, we recently defined for 8 different ANCA test systems assayspecific test results that corresponded to a LR of 0.1, 1, 10 and 30 (24). For the different assays, the test result that corresponded to a LR of 10 was 35 Units, 48.5 CU, 8.6 IU/mL, 2.8 AI, 10 IU/mL, 13.8 U/mL, 48 U/mL and 10.7 IU/mL (24).…”

“…It has been realized that expressing results in the form of LRs provides a convenient way to harmonize test results which otherwise would be expressed in various units and provider-defined scales, making it difficult to compare results. This has led to a proposal for harmonization of antineutrophil cytoplasmic antibody (ANCA) testing (23,24), antinuclear antibody testing (25,26) and autoimmunity tests in general by reporting test result-specific LRs (27,28). The calculation of LRs of test result intervals has been further extended to arbitrary quantitative test results (29, 30) and applied, for example, for the diagnosis of Alzheimer's disease (31), ANCA testing (24), antinuclear antibody testing (26) and celiac disease (22).…”