Background/Purpose:

Recently adipokines have been implicated for their role in regulating immune and inflammatory responses in autoimmune disease. To test the hypothesis that adipokines are predictive of dermatomyositis (DM) disease activity and inflammatory response, we analyzed blood cell gene expression of four adipokines, adiponectin (ADIPOQ), visfatin (NAMPT), leptin (LEP), and resistin (RETN) in juvenile (JDM) and adult (DM) patients.

Methods:

For this study PAXgene vacutainers were collected for 14 DM, 23 JDM, and for adult (n = 5), and pediatric (n = 6) non-inflammatory controls. The IMACS core set myositis disease activity measure for physician global visual analog scale (Global VAS) scores (0-10 cm) was collected for myositis cases at time of blood draw. Total RNA was isolated with on-column DNase treatment according to manufacturer’s protocol (PreAnalytiX). The expression levels of ADIPOQ, NAMPT, LEP, RETN, IL6, and housekeeping genes GAPDH, B2M, and ACTB were generated using a custom RT² Profiler PCR Array. Genes were first normalized to the mean of three housekeeping genes. Relative quantification of gene expression was then normalized to the mean of adult and pediatric controls respectively Wilcoxon tests and Spearman Correlation methods were used for analysis.

Results:

The mean(range) age(years) and gender are as follows: JDM 9.7(3.7-17.1) (65% female), DM 50.1(23.0-72.8)(79% female), pediatric controls 12.4(8.2-16.5)(50% female), adult controls 39.8(25.2-61.4)(60% female). DM and control groups were Caucasian. The JDM group can be described as follows; 68.2% Non-Hispanic, 9.1% African American, 4.5%, American Indian, 4.5% Indian, 4.5% Middle Eastern, 4.5% Pacific Islander, and 4.5% unknown. In this population 79% of DM and 35% of JDM cases were receiving prednisone or an equivalent. Median BMI in the DM group was 25.9(19.7 – 51.2) and 17.2(13.8 -30.0) in JDM (median percentile 65.5(range 2-99)).

LEP, RETN, and NAMPT, all adipokines thought to promote inflammation were consistently up-regulated in all myositis cases compared to all controls, p=0.036, p=0.046 and p=0.013 (Table 1). ADIPOQ, known to have both anti- and pro- inflammatory effects in RA and SLE, did not appear to be dysregulated in the cases. p=0.400(Table 1).   Increased RETN correlated with elevated disease activity represented by Global VAS in our myositis population (r=0.39, p=0.017). The magnitude of change in gene expression still held when groups were separated into juvenile and adult categories however statistical significance was not reached.

Conclusion:

Elevated adipokines levels in JDM and DM may serve as beneficial biomarkers that allow a practitioner to better monitor disease activity and potentially predict disease flares.

Table 1: Relative Quantification of Adipokines in DM and JDM