Diagnosis of Rheumatoid Arthritis May Vary According to Specific Assay Used

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Technical differences in diagnostic tests may affect diagnosis of rheumatoid arthritis, according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria classification.

Rheumatoid arthritis (RA) classification according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria may vary when different assays are used, according to results published in the Annals of the Rheumatic Diseases.

The researchers contributed these variations to “poor harmonization” of rheumatoid factor (RF) and anticyclic citrullinated protein/peptide antibody (ACPA) assays and of test result interpretation.

The study included 594 patients who underwent laboratory testing for a rheumatologic disease for the first time between January 2014 and June 2015. The researchers categorized the patients into 3 groups: RA (n=44), rheumatologic disease control group (n=247), and disease control group (n=225). The researchers interviewed an additional 26 patients who had been newly diagnosed with RA.

The researchers used 6 commercial RF and 7 commercial ACAP assays:

  • Quantia RF on the Abbott ARCHITECT c System
  • QUANTA Lite RF IgM ELISA on a QUAN- TA-Lyser 2
  • RF EliA IgM on Phadia 250
  • RF-II on a Cobas c502 analyzer
  • Diagam RF on a ZENIT analyzer
  • RF IgM ELISA from Euroimmun
  • ARCHITECT Anti-CCP assay on the ARCHI- TECT i System
  • Immunoscan CCPlus on a QUANTA-Lyser 2
  • QUANTA Flash CCP3 on the BIO-FLASH instrument
  • CCP EliA IgG on Phadia 250
  • Anti-CCP on a Cobas e601 analyzer
  • ZENIT RA CCP on a ZENIT analyzer
  • Anti-CCP ELISA from Euroimmun

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For all assays, the likelihood ratio for diagnosing RA increased with increasing antibody levels. The areas under the curve of receiver operating characteristic analysis of the RF (range, 0.676-0.709) and ACPA assays (range, 0.672-0.769) only differed between some ACPA assays. However, when the researchers used the cut-off proposed by the manufacturer, they found large variation in sensitivity and specificity between assays.

“[We] found that for some patients disease classification depended on the RF and/or ACPA assay used,” the researchers wrote. “This further illustrates the need to align clinical interpretation of test results between companies. Correct classification and diagnosis is important to initiate adequate treatment and to exclude self-limiting arthritis and avoid inappropriate treatment.”


Van Hoovels L, Jacobs J, Vander Cruyssen B, et al. Performance characteristics of rheumatoid factor and anti-cyclic citrullinated peptide antibody assays may impact ACR/EULAR classification of rheumatoid arthritis [published online January 23, 2018]. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-212365