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B-cell Receptor Clones Predict High Risk for Rheumatoid Arthritis
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CHICAGO — A high number of dominant B-cell receptor clones in peripheral blood can predict significant short-term risk for rheumatoid arthritis in patients, according to data presented at the ACR/ARHP 2018 Annual Meeting.
“If early treatment is so very important, should we start treatment during the at-risk phase in order to prevent rheumatoid arthritis?” Niek de Vries, MD, PhD, of the University of Amsterdam, asked attendees. “The problem is, only a subset of these patients will develop arthritis within the upcoming 3 years — and it’s only 28%, so less than one-third of the population. We need to know better whom to treat and who we should identify as pre-RA.”
To test and evaluate the predictive value of B-cell receptor clones among individuals at risk for RA, de Vries and colleagues conducted a prospective cohort study of 129 patients at the Reade medical center in Amsterdam. The researchers analyzed the B-cell receptor repertoire in the peripheral blood of participants, all of whom were at risk for RA.
B-cell receptor clones expanded beyond 0.5% of the total repertoire were defined as “highly expanded clones,” shortly characterized as dominant clones. Patients were labeled B-cell receptor–positive if their peripheral blood demonstrated at least five dominant B-cell-receptor clones at baseline.
According to de Vries and colleagues, the number of dominant B-cell receptor clones in peripheral blood at baseline was increased among patients at risk for RA who develop arthritis within 3 years (mean 10.5 ± 5.2), compared with at-risk individuals who do not (2.0 ± 2.4; P < .0001). No at-risk participants who were B-cell receptor–negative developed arthritis at 3 years.
Meanwhile, 71% of those both at-risk and B-cell-receptor-positive were ultimately diagnosed with arthritis by year 3 (estimated RR = 120.1; 95%, CI 7.5-19.17). Using logistic regression, the researchers found that the B-cell receptor clone test performed significantly better in predicting arthritis than the Risk Rule Model.
In addition, a higher number of B-cell receptor clones was linked to an even higher risk for arthritis. This association was maintained even when the analysis was restricted to the B-cell receptor–positive group (P = .019). After dividing the positive cohort into two equal groups, separating those with five to eight highly expanded clones from those with nine or more, a Cox proportional hazard analysis found a significantly greater risk for arthritis at 3 years among those with a high amount of B-cell receptor clones, compared with those with a medium amount (P = .006). Demonstrating nine or more highly expanded clones corresponded with a positive predictive value of 91%.
“B-cell-receptor-test negative individuals can be reassured — in this group, risk for arthritis is similar to background population risk,” de Vries said. “The B-cell-receptor test performs better than clinical parameters, with quick identification of true RA-risk individuals. A positive test in blood predicts imminent onset of RA in high-risk individuals with high accuracy and could be an indication for treatment to prevent disease.” – by Jason Laday
Disclosure: de Vries reports professional relationships with GSK, Janssen, Pfizer and Roche, as well as consulting fees from UCB and MSD.
Reference:
de Vries N. Abstract 835. Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.