Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Type I Interferon-Related Biomarkers Predict Clinical Disease Activity in Inflammatory Myositis.

Reed1,  Ann M., Crowson1,  Cynthia S., Bilgic2,  Hatice, Gillespie2,  Emily Baechler, Hein1,  Molly, Ytterberg1,  Steven R., Amin1,  Shreyasee

Mayo Clinic, Rochester, MN
University of Minnesota, Minneapolis, MN

Background/Purpose:

Biomarkers are needed that are sensitive to disease activity during treatment for juvenile and adult dermatomyositis (DM). DM subjects carry distinct immune Type I interferon (IFN)-inducible gene and chemokine signatures in peripheral blood, which are correlated cross-sectionally with disease activity. We evaluated whether changes in peripheral blood IFN-inducible gene and chemokine scores may serve as novel biomarkers for treatment-independent change in DM disease activity.

Methods:

We followed 51 patients with juvenile (mean age 8 yrs; n=21) and adult (mean age 45 yrs; n=30) DM prospectively for 2 study visits separated by 3–6 months. At each visit, peripheral blood was collected, and clinical data were recorded regarding medication use and disease activity (global, muscle, and extra-muscular) each assessed using a 10 cm visual analog scale (VAS). The whole-blood Type I IFN gene score was defined by expression levels of 3 IFN-regulated genes (IFIT1, G1P2, IRF7) measured by quantitative real-time RT-PCR. Multiplexed immunoassays were used to quantify serum levels of pro-inflammatory cytokines including IL-6, and of Type I IFN-regulated chemokines (I-TAC, IP-10, MCP-1; together yielding a derived IFN chemokine score). Spearman partial correlation methods were used to correlate changes in disease activity with changes in analytes adjusting for medication use.

Results:

The median global disease activity for the total DM cohort at visit 1 was 26 (range 0–80) and median change in global disease activity (visit 2-visit 1) was -13 (range -69, 45). We found strong positive correlations between change in global and muscle disease activity and change in Type 1 IFN chemokine scores (see Table). These measures were correlated both before and after adjustment for medication use. Furthermore, decreasing levels of cytokines and chemokines were highly correlated with a decrease in disease activity, even after medication adjustment (p<0.001–0.009). No differences in results were seen between juvenile and adult DM subgroups.

Cytokine or ChemokineNSpearman Partial Correlation Coefficient After Adjustment for Medication Use (p-value)
Global VASMuscle VASExtra-muscular VAS  
IL-6510.39 (0.009)0.49 (0.001)0.31 (0.049)
IP-10510.48 (0.001)0.45 (0.003)0.48 (0.002)
ITAC510.42 (0.004)0.53 (<0.001)0.45 (0.003)
MCP-1510.32 (0.032)0.46 (0.002)0.33 (0.036)
IFNg50-0.11 (0.48)-0.26 (0.10)-0.06 (0.72)
IL-1b50-0.22 (0.16)-0.12 (0.47)-0.14 (0.38)
IL-8500.37 (0.016)0.50 (<0.001)0.31 (0.055)
TNFa500.32 (0.040)0.48 (0.001)0.28 (0.085)
MCP-2410.29 (0.095)0.51 (0.002)0.16 (0.39)
IFN gene score490.26 (0.096)0.41 (0.007)0.19 (0.25)
IFN chemokine Score*510.50 (<0.001)0.55 (<0.001)0.52 (<0.001)
* IFN chemokine score contains: IP-10, I-TAC and MCP-1.

Conclusion:

Changes in whole blood Type I IFN gene and chemokine signatures, as well as in levels of T-cell cytokines IL-6, IL-8 and TNFa, are highly correlated with changing DM disease activity irrespective of medication use.

To cite this abstract, please use the following information:
Reed, Ann M., Crowson, Cynthia S., Bilgic, Hatice, Gillespie, Emily Baechler, Hein, Molly, Ytterberg, Steven R., et al; Type I Interferon-Related Biomarkers Predict Clinical Disease Activity in Inflammatory Myositis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :820
DOI:

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