medwireNews: Neutrophil-derived biomarkers correlate with disease activity and can predict joint space narrowing and erosive disease among patients with rheumatoid arthritis (RA), researchers report.
Christian Lood (University of Washington, Seattle, USA) and colleagues demonstrated that levels of calprotectin – a marker of neutrophil activation – were significantly higher in plasma and serum samples from RA patients versus matched controls in three separate cohorts.
The first two cohorts were both cross-sectional and included RA patients (n=101 and n=93) and age- and gender-matched controls (n=20 and n=100, respectively), while the third was a RA inception cohort of 247 individuals who were followed up for a median of 8.3 years.
The investigators report that calprotectin levels correlated significantly with markers of RA disease activity in the first cross-sectional cohort, including tender and swollen joint counts (correlation coefficient=0.49), CDAI score (correlation coefficient=0.53), and C-reactive protein (CRP; correlation coefficient=0.62).
And area under the receiver operating characteristic curve analysis demonstrated that calprotectin performed better than CRP for identifying patients with active disease, at an accuracy of 79% versus 70%.
Lood et al combined calprotectin with anti-citrullinated protein antibodies (ACPA), a biomarker known to predict the development of erosive disease, and found that positivity for both markers was a stronger predictor of erosive disease and joint space narrowing than positivity for either marker alone.
Indeed, patients positive for calprotectin and ACPA had a 5.6-fold higher risk for erosive disease and a 3.5-fold higher risk for joint space narrowing than those with only calprotectin positivity, while dual positivity was associated with a 6.0- and 2.0-fold higher risk for erosive disease and joint space narrowing, respectively, compared with ACPA positivity alone.
Therefore, “calprotectin, in combination with ACPA, may improve on the ability to identify patients prone to developing erosive disabling disease, including joint space narrowing,” write the study authors in Arthritis & Rheumatology.
“This is an important finding which may allow for closer monitoring and expedited and aggressive treatment of these patients to avoid disabling disease progression which may be permanent, and improve on their quality of life,” they add.
The researchers also found that neutrophil extracellular traps (NETs) – markers of neutrophil cell death – were “markedly elevated” among individuals with RA compared with controls, and NET positivity could predict active disease versus remission among those with seropositive RA, with a sensitivity and specificity of 68.6% and 75.0%, respectively.
Together, these findings “highlight the essential role of neutrophils in the RA pathogenesis and support development of therapies targeting neutrophil-mediated inflammation in these patients,” conclude Lood and team.
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Arthritis Rheumatol 2019; doi:10.1002/art.41062