Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Previous reports have identified a number of pro-inflammatory cyto/chemokines as candidate activity-specific SLE biomarkers. In our preliminary studies we found that out of a panel of 20 common cyto/chemokines examined, only MCP-1, IP-10, sVCAM and adiponectin were preferentially elevated in patients with active as compared to inactive disease. In this study, the relationship between fluctuations in disease activity and these four cyto/chemokines was examined to determine their utility in predicting fluctuations (exacerbation or improvement) in disease activity.
Methods: SLE patients (n = 55) satisfying 4 or more ACR criteria were recruited and followed over a 14-month period with a minimum of 3 clinical and biochemical assessments over that time. The plasma concentration of the 4 analytes was determined by Luminex assay. Disease activity was determined by the SLEDAI-2K (S-2K). A modified SLEDAI-2K (mS-2K) was calculated by subtracting the contribution of anti-dsDNA antibodies and complement (C3) from the global score. Variation between visits was examined with a change in S-2K of ± 4 between two consecutive visits deemed a clinically significant event. Event classification was compared with analyte levels using a one-way ANOVA followed by visualization. The ability of analyte levels to forecast disease activity was evaluated using a leave-one-out cross-validation analysis.
Results: Analysis of all available assessments showed a statistically significant positive correlation between adiponectin (Spearman’s rho (r) = 0.25, p < 1 x 10-3), VCAM (r = 0.24, p < 1 x 10-3) and IP-10 (r = 0.21, p = 2 x 10-3) and global disease activity as defined by the mS-2K. These correlations were comparable to the performance of traditional biomarkers; anti-dsDNA antibodies (r = 0.22, p < 1 x 10-3) and complement (C3, r = -0.24, p < 1 x 10-3). The relationship between meaningful fluctuations in disease status between consecutive visits and biomarker levels was examined. Changes in disease state were exclusively reflected in changes in sVCAM-1 (p = 0.04) and adiponectin (p = 0.05). Both traditional biomarkers (anti-dsDNA antibodies and C3) and other tested cytokines (MCP-1, IP-10) did not reflect fluctuations in disease state. The ability of these biomarkers to predict a clinically meaningful change in disease status within 3 to 6 months of assessment was also assessed. In our analysis < 10% of events were accurately predicted.
Conclusion: These results suggest that despite their early promise, and evidence that some of the selected cyto/chemokines fluctuate with disease activity, none of the analytes examined could accurately forecast clinically significant changes in disease state.
Disclosure:
C. landolt-Marticorena,
None;
S. Prokopec,
None;
S. Morrison,
None;
H. Reich,
None;
J. Scholey,
None;
D. D. Gladman,
Abbott, Bristol-Myers Squibb, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma,
2,
Abbott, Bristol-Myers Squibb, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma,
5;
M. B. Urowitz,
None;
P. Boutros,
None;
P. R. Fortin,
None;
J. E. Wither,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fluctuations-in-svcam-1-and-adiponectin-mirror-fluctuations-in-disease-activity-in-lupus-but-cannot-be-use-to-accurately-predict-impending-changes-in-disease-state/