Abstract 2056: IFN-regulated chemokines are reliable biomarkers of systemic lupus erythematosus disease activity.
Authors:
JW Bauer, M Petri, FM Batliwalla, J Wilson, C Slattery, S Singh, H Tesfasyone, PK Gregersen, TW Behrens, EC Baechler.
Background:
About 50% of SLE patients have the interferon gene signature, meaning that a large group of interferon regulated genes have been up-regulated. This gene signature has been associated with having low complement, high anti-dsDNA, leucopenia, and renal disease. However, the interferon gene response doesn’t change over time or predict flares. This study asked whether interferon-associated chemokines might be better markers of disease activity.
Methods:
288 SLE patients, part of the Hopkins Lupus Cohort, were followed quarterly for 1 year. At each visit, disease activity was measured using the Physician’s Global Assessment on a 0 to 3 visual analog scale, and the SELENA revision of the SLEDAI. Based on a small previous study, 3 interferon-regulated chemokines: IP-10, MCP-1, and MIP 3B were studied. The chemokine score was the sum of the normalized values.
Results:
The first comparison was of active (SLEDAI > 6) SLE versus inactive (SLEDAI < 1 and PGA = 0). “Chemokine high” scores were associated with higher SLEDAI.
The second analysis was of change over time. Flare was defined as SLEDAI > 3. Chemokine scores rose with flare (and C3, C4, anti-dsDNA, and ESR did not change). Improvement was defined as a decrease in SLEDAI of 3 or more points. The chemokine score was reduced with improvement (ESR, C3, C4 changed as well – but less so).
In the final analysis, the baseline chemokine score was predictive of flare.
Conclusion:
The authors concluded that these 3 chemokines might be useful in monitoring therapy and in clinical decision making.
Editorial Comment:
Chemokines are important in WBC migration and lymphoid architecture. In this study, the 3 chosen chemokines out-performed some “classic” markers of serologic activity, such as anti-dsDNA and low complement.
An important question is whether they will be equally useful in all organ systems. Secondly, if they predict only 50% of flares, will clinicians be willing to treat presumptively based on the chemokine score?
These results now need to be replicated in an independent data set. It would be incredibly important to see how they perform in clinical trials of anti-interferon therapy.
