Session Type: ACR Plenary Session
Session Time: 11:00AM-12:30PM
Background/Purpose: A phase characterized by the presence of specific autoantibodies and arthralgias in the absence of clinically evident synovial inflammation often precedes the onset of rheumatoid arthritis (RA). However, only a subset of these RA-risk individuals will develop active disease in the short term.1 Recent findings show that dominant B-cell receptor (BCR) clones in peripheral blood can accurately predict imminent onset of arthritis in these RA-risk individuals.2 To validate the predictive role of BCR clones in peripheral blood in RA-risk individuals and explore it in more detail in a larger cohort.
Methods: The BCR repertoire in peripheral blood was analysed using next-generation BCR sequencing in a prospective cohort study of 129 RA-risk individuals from Reade. Like earlier, BCR clones expanded beyond 0.5% of the total repertoire were labelled highly expanded clones (HECs), shortly referred to as dominant BCR clones, and individuals were labelled BCR-positive if peripheral blood at study baseline showed ≥ 5 dominant BCR clones.
Results: We confirmed that the number of dominant BCR clones in peripheral blood at baseline is increased in RA-risk individuals who develop arthritis within 3 years, compared to RA-risk individuals who do not (10.5 ± 5.2 vs. 2.0 ± 2.4; mean ±SD; p<0.0001). Within 3 years none of the BCR-negative RA-risk individuals developed arthritis, while 32 (71%) of the BCR-positive individuals did (estimated RR: 120.1; 95%-CI: 7.5 – 1917; p<0.0001). Using a logistic regression the BCR clone test performed significantly better in predicting development of arthritis in comparison with the Risk Rule Model, a test consisting of clinical parameters (DAIC= 14.91).3
A higher number of BCR clones was associated with an even higher risk of arthritis, even when this analysis was restricted to the BCR-positive group (Spearman R, p=0.019). When we divided the BCR clone positive individuals into two equal groups (5-8 HECs: n=23 and ≥ 9 HECs: n=22 ) cox proportional hazard analysis showed a significantly higher risk of arthritis at 3 years in the BCR-high versus BCR-medium group (log-rank test p=0.006). Having 9 or more HECs corresponded with a positive predictive value of 91% (20 in 22).
Conclusion: High short-term risk of rheumatoid arthritis is predicted by a high number of dominant BCR clones at baseline. Among the 17% high-risk individuals 91% (20 in 22) developed arthritis within 3 years, after a median follow-up of 16 months. Our data support therapeutic intervention in this high-risk group.
1Bos, WH et al. Ann. Rheum. Dis. 2010;69:490-4, 2Tak, PP et al. Ann. Rheum. Dis. 2017;76: 1924-30, 3van de Stadt, LA et al. Ann. Rheum. Dis. 2013;72:1920-6
To cite this abstract in AMA style:Musters A, van Beers-Tas M, Doorenspleet ME, Klarenbeek PL, van Schaik BCD, van Kampen AHC, Baas F, van Schaardenburg D, de Vries N. Identifying Individuals with High Risk for Imminent Onset of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/identifying-individuals-with-high-risk-for-imminent-onset-of-rheumatoid-arthritis/. Accessed April 8, 2020.
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