Session Information
Session Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity
Session Type: Abstract Submissions (ACR)
Background/Purpose
HMGB1 (High Mobility Group Box 1), a non-histone nuclear protein, is a prototypic alarmin that displays immunological activity following release during cell death or immune cell activation. As shown in studies of patients with rheumatoid arthritis (RA) and animal models, HMGB1 plays a key role in pathogenesis; HMGB1 has increased expression in synovial tissue and blockade of HMGB1 can attenuate disease in animal models. While the role of HMGB1 in mediating disease has been well studied, its role as a biomarker has received less attention. The present study therefore explored the expression of HMGB1 in the blood of RA patients, investigating correlations with various clinical features.
Methods
This study utilized samples from the RACER (Rheumatoid Arthritis Comparative Effectiveness Research) cohort. Patients varied in disease duration and received therapy determined by clinical response. Disease activity was assessed by DAS 28 scores using C-reactive protein as the acute phase reactant. The samples, selected to provide a range of disease activity, were divided into 4 groups: remission; low activity; moderate activity; and high activity. Levels of HMGB1 were determined by ELISA using the Shino-test kit. The concentrations of HMGB1 in the plasma from 10, non-RA control subjects were also measured.
Results
Among 100 patients with RA, HMGB1 levels varied from 1.1 to 19.3 ng/ml (median value = 5.73 ng/ml) which was significantly higher than those of the control population (range = 0.72-3.28; median value = 1.93 ng/ml). Despite the increase in HMGB1 levels in the RA population, the median values of the 4 disease activity groups were similar (remission, 5.98; low 5.09; moderate 5.64; high, 6.02). These differences did not reach statistical significance by a non-parametric ANOVA. In contrast, CRP levels showed a statistically significant association with disease activity by a non-parametric ANOVA (<0.0001). As a previous study suggested a relationship with disease duration, the results were analyzed in terms of duration less than 5 years, 5-10 years, 15-20 years and greater than 20 years. This analysis failed to reveal a relationship with disease duration. Values of males and females were also similar.
Conclusion
These studies demonstrate that levels of HMGB1 are elevated in the blood of patients with RA and show a relationship to disease activity distinct from that of CRP. As HMGB1 levels were increased in patients either in remission or with low disease activity, these findings suggest ongoing inflammation that may not be apparent with either the DAS 28 or CRP. Furthermore, since HMGB1 can also arise from cell death, the elevation of HMGB1 levels, even with remission or low disease activity, may reflect tissue destruction that persists even with inflammation restrained.
Disclosure:
D. S. Pisetsky,
None;
D. Spencer,
None;
S. R. Wisniewski,
None;
J. Lyons,
None;
M. Saul,
None;
M. J. McGeachy,
None;
Y. G. Hwang,
None;
H. Eng,
None;
L. W. Moreland,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-relationship-between-disease-activity-and-levels-of-hmgb1-in-patients-with-rheumatoid-arthritis/