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

Lieve Van Hoovels, Bert Vander Cruyssen, Daniela Sieghart, Carolien Bonroy (UGent) , Eszter Nagy, Rille Pullerits, Sasa Cucnik, Charlotte Dahle, Ingmar Heijnen, Luca Bernasconi, et al.
(2022) RMD OPEN. 8(1).
Author
Organization
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
rheumatoid factor, rheumatoid arthritis, anti-citrullinated protein antibodies, CLASSIFICATION CRITERIA, AMERICAN-COLLEGE, RHEUMATOLOGY/EUROPEAN LEAGUE, LIKELIHOOD RATIOS, ARTHRITIS, CONSENSUS, OSTEOARTHRITIS, PERFORMANCE, ASSAYS

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Citation

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MLA
Van Hoovels, Lieve, et al. “Multicentre Study to Improve Clinical Interpretation of Rheumatoid Factor and Anti-Citrullinated Protein/Peptide Antibodies Test Results.” RMD OPEN, vol. 8, no. 1, 2022, doi:10.1136/rmdopen-2021-002099.
APA
Van Hoovels, L., Vander Cruyssen, B., Sieghart, D., Bonroy, C., Nagy, E., Pullerits, R., … Bossuyt, X. (2022). Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results. RMD OPEN, 8(1). https://doi.org/10.1136/rmdopen-2021-002099
Chicago author-date
Van Hoovels, Lieve, Bert Vander Cruyssen, Daniela Sieghart, Carolien Bonroy, Eszter Nagy, Rille Pullerits, Sasa Cucnik, et al. 2022. “Multicentre Study to Improve Clinical Interpretation of Rheumatoid Factor and Anti-Citrullinated Protein/Peptide Antibodies Test Results.” RMD OPEN 8 (1). https://doi.org/10.1136/rmdopen-2021-002099.
Chicago author-date (all authors)
Van Hoovels, Lieve, Bert Vander Cruyssen, Daniela Sieghart, Carolien Bonroy, Eszter Nagy, Rille Pullerits, Sasa Cucnik, Charlotte Dahle, Ingmar Heijnen, Luca Bernasconi, Farid Benkhadra, Laura Bogaert, Stefanie Van den Bremt, Ann Van Liedekerke, Geert Vanheule, Johan Robbrecht, Lucy Studholme, Claudine Wirth, Ruediger Mueller, Diego Kyburz, Christopher Sjowall, Alf Kastbom, Rok Jese, Boja Jovancevic, Emese Kiss, Peggy Jacques, Daniel Aletaha, Guenter Steiner, Patrick Verschueren, and Xavier Bossuyt. 2022. “Multicentre Study to Improve Clinical Interpretation of Rheumatoid Factor and Anti-Citrullinated Protein/Peptide Antibodies Test Results.” RMD OPEN 8 (1). doi:10.1136/rmdopen-2021-002099.
Vancouver
1.
Van Hoovels L, Vander Cruyssen B, Sieghart D, Bonroy C, Nagy E, Pullerits R, et al. Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results. RMD OPEN. 2022;8(1).
IEEE
[1]
L. Van Hoovels et al., “Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results,” RMD OPEN, vol. 8, no. 1, 2022.
@article{8761297,
  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.}},
  articleno    = {{e002099}},
  author       = {{Van Hoovels, Lieve and Vander Cruyssen, Bert and Sieghart, Daniela and Bonroy, Carolien and Nagy, Eszter and Pullerits, Rille and Cucnik, Sasa and Dahle, Charlotte and Heijnen, Ingmar and Bernasconi, Luca and Benkhadra, Farid and Bogaert, Laura and Van den Bremt, Stefanie and Van Liedekerke, Ann and Vanheule, Geert and Robbrecht, Johan and Studholme, Lucy and Wirth, Claudine and Mueller, Ruediger and Kyburz, Diego and Sjowall, Christopher and Kastbom, Alf and Jese, Rok and Jovancevic, Boja and Kiss, Emese and Jacques, Peggy and Aletaha, Daniel and Steiner, Guenter and Verschueren, Patrick and Bossuyt, Xavier}},
  issn         = {{2056-5933}},
  journal      = {{RMD OPEN}},
  keywords     = {{rheumatoid factor,rheumatoid arthritis,anti-citrullinated protein antibodies,CLASSIFICATION CRITERIA,AMERICAN-COLLEGE,RHEUMATOLOGY/EUROPEAN LEAGUE,LIKELIHOOD RATIOS,ARTHRITIS,CONSENSUS,OSTEOARTHRITIS,PERFORMANCE,ASSAYS}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{10}},
  title        = {{Multicentre study to improve clinical interpretation of rheumatoid factor and anti-citrullinated protein/peptide antibodies test results}},
  url          = {{http://doi.org/10.1136/rmdopen-2021-002099}},
  volume       = {{8}},
  year         = {{2022}},
}
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