Cover Page
The handle
http://hdl.handle.net/1887/136529
holds various files of this Leiden
University dissertation.
Author:
Brinck, R.M. ten
Title:
Comprehending the symptomatic phase preceding rheumatoid arthritis: Clinically
suspect arthralgia
Chapter 4
Screening for two or three
autoantibodies in persons at risk for
RA – implications of current data for
clinical practice
R.M. ten Brinck 1, L.A. Trouw 2, Annette H.M. van der Helm–van Mil 1,3
1. Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands
2. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
3. Department of Rheumatology, Erasmus Medical Centre, Rotterdam, The Netherlands
Published as:
74 Chapter 4
Sir,
In recent years, research has focused on identifying novel autoantibodies and their value for early identification of rheumatoid arthritis (RA). A frequently studied novel autoantibody is anti-carbamylated protein (anti-CarP)[1,2] Presence of this autoantibody at diagnosis of RA is associated with a higher disease activity and a more destructive disease course. [3] The literature on the value of this autoantibody, in addition to the evaluation of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), in persons at risk for RA was recently meta-analyzed.[4] It was demonstrated that combined presence of ACPA, RF and anti-CarP rarely occurred in control groups and therefore was highly specific for RA. Although promising, three issues need to be considered before it can be concluded that assessing three autoantibodies in the same individuals is more beneficial than evaluation of ACPA and RF only.
4
To address these issue in patients that are considered to be in the symptomatic pre-arthritis phase, we performed additional analyses in our longitudinal cohort study on consecutive patients that presented with Clinically Suspect Arthralgia (CSA)[7] to evaluate the diagnostic accuracy of three positive autoantibodies for RA development.
76 Chapter 4
Based on these data, the added value of testing anti-CarP as a third autoantibody in arthralgia patients presenting at secondary care would seem limited. Importantly, these data cannot be extrapolated to the setting of populations without symptoms. Future population-based longitudinal studies will have to demonstrate if a combination of three autoantibodies can contribute to the identification of at-risk patients in the stage preceding the onset of arthralgia.
4
Figure 1. Kaplan-Meier plot presenting no difference in
progression to RA in patients with Clinically Suspect Arthralgia
Legend:
78 Chapter 4
References
1 Verheul MK, Shiozawa K, Levarht EWN, et al. Anti-carbamylated protein antibodies in rheumatoid arthritis patients of Asian descent. Rheumatology 2015;54:1930–2. doi:10.1093/
rheumatology/kev250
2 Shi J, Knevel R, Suwannalai P, et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proceedings of the National Academy of Sciences 2011;108:17372–7. doi:10.1073/ pnas.1114465108
3 Truchetet M-E, Dublanc S, Barnetche T, et al. Association of the Presence of Anti–Carbamylated Protein Antibodies in Early Arthritis With a Poorer Clinical and Radiologic Outcome. Arthritis & Rheumatology 2017;69:2292–302. doi:10.1002/art.40237
4 Verheul MK, Böhringer S, van Delft MAM, et al. The combination of three autoantibodies, ACPA, RF and anti-CarP antibodies is highly specific for rheumatoid arthritis: implications for very early identification of individuals at risk to develop rheumatoid arthritis. Arthritis & Rheumatology Published Online First: 21 May 2018. doi:10.1002/ art.40562
5 Rutjes AWS, Reitsma JB, Vandenbroucke JP, et al. Case-Control and Two-Gate Designs in Diagnostic Accuracy Studies. Clinical Chemistry 2005;51:1335–41. doi:10.1373/clinchem.2005.048595 6 Rutjes AWS, Reitsma JB, Di Nisio M,
et al. Evidence of bias and variation in diagnostic accuracy studies. Canadian Medical Association Journal 2006;174:469–76. doi:10.1503/cmaj.050090
7 ten Brinck RM, van Steenbergen HW, van Delft MAM, et al. The risk of individual autoantibodies, autoantibody combinations and levels for arthritis development in clinically suspect arthralgia. Rheumatology 2017;56:2145– 53. doi:10.1093/rheumatology/kex340 8 van Steenbergen HW, Mangnus L,
