Newly Licensed Test Finds ACPA-Negative Patients With Early RA


Filling in the gap left by ACPA-negative results in patients with early rheumatoid arthritis, a research team has now licensed a new biomarker for detection of a similar, but importantly different, biomarker called anti-CarP. It detects antibodies to carbamylated, rather than citrullinated, proteins.

A team that has been in the forefront of research surrounding anti-citrullinated protein antibodies (ACPA) in the detection of early rheumatoid arthritis (RA) has now licensed a similar biomarker that tests positive in many ACPA-negative patients, and appears to predict a more severe course of disease. The test measures antibodies to carbamylated protein (anti-CarP), which differs from ACPA by detecting homocitrulline rather than citrulline -- a difference of only one methyl group, but apparently an important one.

"Understanding which patients would benefit most from [early] intervention is important to maximize efficiency, and detection of anti-CarP antibodies may identify such patients," said Tom Huizinga MD, chairman of rheumatology at Leiden University Medical Center in the Netherlands, in a press release announcing the licensing agreement with INOVA Diagnostics of San Diego.

A study published by the team last year in Proceedings of the National Academy of Sciences showed that antibodies recognizing CarP were present in about 50% of RA patients. Importantly, they are detected in up to 30% of ACPA-negative patients, and correlate with increased joint damage.

As opposed to citrullination, which converts the amino acid arginine to citrulline, carbamylation converts another amino acid, lysine, to homocitrulline. Smoking, which is associated with RA risk, is known to increase levels of the enzyme that catalyzes carbamylation; the reaction also takes place extensively during chronic inflammation.

The Leiden team reported last December that anti-CarP readings were positive in 39% of 340 arthralgia patients without clinical signs of arthritis, and that the presence of these antibodies was associated with the development of RA in these patients even after correction for rheumatoid factor (RF) and ACPA status.

In announcing the licensing agreement, team members expressed hope that further research into anti-CarP will lead to new insights into RA pathogenesis and perhaps to new treatments. Whether it will resolve or muddle the still-open question about the relative merits of ACPA and RF remains to be seen.

"Yet another test may allow some further information," observed Josef Smolen MD, chairman of the Division of Rheumatology at the Medical University of Vienna, "but it will have to be checked by others and related to RF, which I think is still highly informative."

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