Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results

Abstract

BackgroundRheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays.Materials and methodsSix total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls.ResultsUsing cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA.ConclusionDefining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays.

Standardisation of ACPA tests: evaluation of a new candidate reference preparation

“…It should be noted that for all assays included in this study, test result interval-specific likelihood ratios have been described. 14 …”

“…The diagnostic performance of the ACPA assays included in this study based on the samples from individuals with RA and who did not have RA was published previously. 14 In short, when the manufacturer’s cut-off was used, the sensitivity ranged from 57.8% to 64.6% and the specificity from 94.9% to 97.8%. When three times the upper limit of normal was used as threshold, the sensitivity ranged from 50.8% to 60.1% and the specificity from 98.0% to 98.5%.…”

“…When three times the upper limit of normal was used as threshold, the sensitivity ranged from 50.8% to 60.1% and the specificity from 98.0% to 98.5%. 14 …”

“…the upper limit of normal was used as threshold, the sensitivity ranged from 50.8% to 60.1% and the specificity from 98.0% to 98.5%. 14 ROC curves were generated with Analyse-it for Microsoft Excel.…”

The mosaic of autoimmunity – Finally discussing in person. The 13th international congress on autoimmunity 2022 (AUTO13) Athens

“…ACPA tests showed higher LRs than RF and %22 RA patients reported to have ACPA levels with LRs more than 80. Revisiting antibody level thresholds and determining test result interval-specific LRs could allow better adjustment of ACPA and RF assays to clinical practice, the authors concluded [ 30 ]. Furthermore, during the autoantibodies session, Mahler hypothesized that autoantibodies do not only aid in diagnosis of autoimmune diseases, rather they may also be useful in classifying patients into disease subgroups [ 31 ].…”