patient care perspectives
Use of 14-3-3η Protein, Multi-Biomarker Disease Activity, and Other Emerging Tests to Profile Patients With Rheumatoid Arthritis
In certain clinical scenarios, new diagnostic tests such as 14-3-3η protein and multi-biomarker disease activity (MBDA) have been shown to offer additive value in the diagnosis and prognosis of patients with rheumatoid arthritis (RA). Such molecular profiling may have useful applications, including in the identification of patients who require less intensive therapy.
Professor of Medicine and Population and Quantitative Health Sciences
“The MBDA score predicts structural progression and might be used to determine which patients may not need more aggressive therapy.”
14-3-3η is a specific isoform of a family of intracellular proteins that are expressed exclusively in eukaryotic cells. These proteins bind to and regulate the biologic activity of more than 200 intracellular proteins and are involved in regulating protein trafficking, cellular signaling, and cytoskeletal transport. 14-3-3η is overexpressed in patients with RA compared with healthy patients and those with osteoarthritis, axial spondyloarthritis, or gout. It induces proinflammatory cytokines, RANKL, and matrix metalloproteinases, which are involved in joint damage, and thus it may predict radiographic progression in patients with early and established RA. 14-3-3η is a biomarker that has been detected in patients who are otherwise seronegative by lacking rheumatoid factor or anti–citrullinated protein antibodies. Further, it may be complementary to these other biomarkers in the diagnosis of RA (eg, the presence of 14-3-3η in addition to rheumatoid factor and/or anti–citrullinated protein antibodies incrementally increases the likelihood of an RA diagnosis). Patients with low baseline levels of 14-3-3η (<0.5 ng/mL) appear to have a lower risk of radiographic progression and may not need medical treatment that is as aggressive as those with higher levels. However, prospective studies are needed to confirm the utility of 14-3-3η as a predictive biomarker.
The MBDA test Vectra DA measures concentrations of 12 biomarkers to generate a score that ranges from 0 to 100. Based on the MBDA score, disease activity categories of remission, low, moderate, and high disease activity have been established. The MBDA score may provide additional utility in assessing RA disease activity to that of individual acute phase reactants, such as the sedimentation rate and C-reactive protein (CRP). Data indicate that the sedimentation rate and CRP are both within the normal range in more than half of patients with active RA, as defined by a Clinical Disease Activity Index score higher than 2.8 (indicating at least low disease activity). Thus, there is a need for a laboratory test that measures more than a single acute phase reactant to assess RA disease activity.
Data from the SWEFOT trial have demonstrated that the baseline MBDA score is a strong predictor of radiographic progression. Among patients with RA with high disease activity (MBDA score >44) despite methotrexate monotherapy, 20.9% exhibited radiographic progression at 1 year compared with 3.4% of those with moderate disease activity (MBDA score 30-44) and none of those with low disease activity (MBDA score <30). These findings indicate that the MBDA score predicts structural progression and might be used to determine which patients may not need more aggressive therapy.
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