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Multicenter Study
. 2022 Mar;8(1):e002099.
doi: 10.1136/rmdopen-2021-002099.

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

Lieve Van Hoovels  1   2 , Bert Vander Cruyssen  3 , Daniela Sieghart  4 , Carolien Bonroy  5   6 , Eszter Nagy  7 , Rille Pullerits  8   9 , Saša Čučnik  10 , Charlotte Dahle  11 , Ingmar Heijnen  12 , Luca Bernasconi  13 , Farid Benkhadra  14 , Laura Bogaert  2 , Stefanie Van Den Bremt  2 , Ann Van Liedekerke  15 , Geert Vanheule  16 , Johan Robbrecht  17 , Lucy Studholme  18 , Claudine Wirth  19 , Rüdiger Müller  20 , Diego Kyburz  21 , Christopher Sjöwall  11 , Alf Kastbom  11 , Rok Ješe  10 , Boja Jovancevic  9 , Emese Kiss  22 , Peggy Jacques  23 , Daniel Aletaha  4 , Guenter Steiner  4   24 , Patrick Verschueren  25   26 , Xavier Bossuyt  27   28
Affiliations
Multicenter Study

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

Lieve Van Hoovels et al. RMD Open. 2022 Mar.

Erratum in

Abstract

Background: Rheumatoid 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 methods: Six 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.

Results: Using 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.

Conclusion: Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays.

Keywords: anti-citrullinated protein antibodies; rheumatoid arthritis; rheumatoid factor.

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Conflict of interest statement

Competing interests: XB, LVH, GS and DS have received speaker fees from and have been a consultant for Thermo Fisher Scientific. LBernasconi and IH have received speaker fees from Thermo Fisher Scientific. DA and PJ are editorial board members of RMD Open. All participating diagnostic companies in-kind supported with RF/ACPA assays and technical training: Thermo Fisher Scientific, Uppsala, Sweden; Cambridge Life Science, Ely, UK; Ortho-Clinical Diagnostics, Raritan, New Jersey, USA; Diagam, Ghislenghien, Belgium; Roche Diagnostics, Mannheim, Germany; Svar Life Science, Malmö, Sweden; Immunodiagnostic Systems, Tyne and Wear, UK; Orgentec, Mainz, Germany; Abbott, Wiesbaden, Germany; Euroimmun, Lübeck, Germany; Bio-Rad Laboratories, Hercules, California, USA; and Siemens Healthineers, Sudbury, UK.

Figures

Figure 1
Figure 1
Box whisker plots of the likelihood ratio of serum rheumatoid factor (RF) for the different test result-specific intervals, delimited by thresholds that correspond to predefined specificities (90.0%, 92.5%, 95.0% and 97.5%). See table 3 for further details. Results are shown for the Beckman Coulter RF assay, but similar results were obtained for the other RF assays included in the study.
Figure 2
Figure 2
Box whisker plots of the likelihood ratio of serum anti-citrullinated protein/peptide antibodies (ACPA) for the different test result-specific intervals, delimited by thresholds that correspond to predefined specificities (90.0%, 97.5%, 99.0% and 99.8%). See table 4 for further details. Results are shown for the Orgentec ACPA assay, but similar results were obtained for the other ACPA assays included in the study.
See this image and copyright information in PMC

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