Easily accessible biomarkers are urgently needed to evaluate immune activation in Juvenile Dermatomyositis (JDM). The goal of this retrospective study is to define immunological and clinical differences between untreated JDM patients with either normal or elevated (>10 mmol/L) levels of neopterin, a biomarker of macrophage activation. We included all JDM with neopterin data obtained before initiating medical therapy. We assessed T, B, NK cell populations, muscle enzymes, and disease activity scores for skin (sDAS), muscle (mDAS), total (tDAS), the duration of untreated disease, disease course, and myositis-specific antibody (MSA). Seventy-nine percent of 139 untreated JDM patients had elevated serum neopterin. The group with elevated neopterin had significantly more active disease: tDAS 11.9 vs. 8.1 (p < 0.0001), mDAS 5.8 vs. 3.1 (p < 0.0001), sDAS 6.1 vs. 4.9 (p = 0.0002), aldolase 24.0 vs. 7.6 U/L (p < 0.0001), von Willebrand factor antigen (p < 0.0001), and ESR 19.8 vs. 11.5 mm/hr (p = 0.01). The flow cytometry documented both reduced T cells (1494 vs. 2278/mm³, p = 0.008) and NK cells (145 vs. 240/mm³, p = 0.003). TNFα-308AA/AG polymorphism was more common in children with elevated neopterin than TNFα-308GG (p 0.05). We conclude that the availability of neopterin data will contribute to the rapid assessment of untreated JDM disease activity.

Glucocorticoids are standard of care for many chronic inflammatory conditions, including juvenile dermatomyositis (JDM) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We sought to define pharmacodynamic biomarkers of therapeutic efficacy and safety concerns of glucocorticoid treatment for these two disorders. Previous proteomic profiling of patients with Duchenne muscular dystrophy (DMD) and inflammatory bowel disease (IBD) treated with glucocorticoids identified candidate biomarkers for efficacy and safety concerns of glucocorticoids. Serial serum samples from patients with AAV (n = 30) and JDM (n = 12) were obtained during active disease, and after treatment with glucocorticoids. For AAV, 8 of 11 biomarkers of the anti-inflammatory response to glucocorticoids were validated (P-value ≤0.05; CD23, macrophage-derived cytokine, interleukin-22 binding protein, matrix metalloproteinase-12, T lymphocyte surface antigen Ly9, fibrinogen gamma chain, angiopoietin-2 [all decreased], and protein C [increased]), as were 5 of 7 safety biomarkers (P-value ≤0.05; afamin, matrix metalloproteinase-3, insulin growth factor binding protein-5, angiotensinogen, leptin [all increased]). For JDM, 10 of 11 efficacy biomarkers were validated (P-value ≤0.05; all proteins except fibrinogen gamma chain) and 6 of 7 safety biomarkers (P-value ≤0.05; AAV proteins plus growth hormone binding protein). The identified efficacy biomarkers may be useful as objective outcome measures for early phase proof-of-concept studies when assessing novel anti-inflammatory drugs in JDM and AAV, and likely in other inflammatory disorders. Similarly, safety biomarkers may also be helpful assessing toxicity of alternatives to glucocorticoids.

Objective: This study determined if an accessible, serologic indicator of vascular disease activity, the von Willebrand factor antigen (vWF:Ag), was useful to assess disease activity in children with juvenile dermatomyositis (JDM), a rare disease, but the most common of the pediatric inflammatory myopathies. Methods: A total of 305 children, median age 10 years, 72.5% female, 76.5% white, with definite/probable JDM at diagnosis, were enrolled in the Ann & Robert H. Lurie Cure JM Juvenile Myositis Repository, a longitudinal database. Disease Activity Score (DAS) and vWF:Ag data were obtained at each visit. These data were analyzed using generalized estimating equation (GEE) models (both linear and logistic) to determine if vWF:Ag reflects disease severity in children with JDM. A secondary analysis was performed for untreated active JDM to exclude the effect of medications on vWF:Ag. Result: The vWF:Ag test was elevated in 25% of untreated JDM. We found that patients with elevated vWF:Ag had a 2.55-fold higher DAS total (CI₉₅: 1.83–3.27, p < 0.001). Patients with difficulty swallowing had 2.57 higher odds of elevated vWF:Ag (CI_95: 1.5–4.38, p < 0.001); those with more generalized skin involvement had 2.58-fold higher odds of elevated vWF:Ag (CI₉₅: 1.27–5.23, p = 0.006); and those with eyelid peripheral blood vessel dilation had 1.32-fold higher odds of elevated vWF:Ag (CI₉₅: 1.01–1.72, p = 0.036). Untreated JDM with elevated vWF:Ag had more muscle weakness and higher muscle enzymes, neopterin and erythrocyte sedimentation rate compared to JDM patients with a normal vWF:Ag. Conclusion: vWF:Ag elevation is a widely accessible concomitant of active disease in 25% of JDM.

In this study, we determined if B lymphocytosis may serve as a JDM biomarker for disease activity. Children with untreated JDM were divided into two groups based on age-adjusted B cell percentage (determined through flow cytometry): 90 JDM in the normal B cell group and 45 in the high B cell group. We compared through T-testing the age, sex, ethnicity, duration of untreated disease (DUD), disease activity scores for skin (sDAS), muscle (mDAS), total (tDAS), CMAS, and neopterin between these two groups. The patients in the high B cell group had a higher tDAS (p = 0.009), mDAS (p = 0.021), and neopterin (p = 0.0365). Secondary analyses included B cell values over time and BAFF levels in matched patients with JM (juvenile myositis) and concurrent interstitial lung disease (ILD); JM alone and healthy controls Patient B cell percentage and number was significantly higher after 3–6 months of therapy and then significantly lower on completion of therapy (p =< 0.0001). The JM groups had higher BAFF levels than controls 1304 vs. 692 ng/mL (p = 0.0124). This study supports B cell lymphocytosis as a JDM disease-activity biomarker and bolsters the basis for B cell-directed therapies in JDM.

Objective: High-dose glucocorticoids (GC) remain the primary therapy to induce remission in Juvenile Dermatomyositis (JDM). Studies of the natural history of GC associated weight gain in children are very limited, especially in the JDM population. This study aims to measure BMI changes in a cohort of JDM subjects over 60 months and to examine the changes in body composition by DXA. Methods: We included all subjects with JDM who had 5 years of follow-up data and multiple DXA studies. BMI and total body fat (TBF) percentiles were calculated based on the CDC published percentile charts. To study the natural history of weight gain and TBF, we assessed the data at four-time points (T0 = baseline, T1 > 1.5 years, T2 = 1.51–3.49 years, T3 = 3.5–5 years). Results: 68 subjects (78% female, 70% white) were included in this retrospective study. Paired T-test showed a significant increase in the mean BMI percentile by 17.5 points (P = 0.004) after the initiation of medical treatment, followed by a gradual decrease over the study period. However, the TBF percentile did not change over the study period. TBF in the last visit (T3) had a strong correlation with the T1 BMI, and T1 TBF percentile (correlation coefficients 0.63, 0.56 P < 0.001, 0.002 respectively). Also, there was a positive correlation (correlation coefficients 0.39, P = 0.002) between the TBF percentile and muscle DAS but not the skin DAS. Conclusions: Although the BMI percentile decreased throughout the study, the TBF percentile remained high until the end of the study (60 months). This finding raises the concern that some of the reduction in the BMI percentile could reflect a drop in the lean body mass from muscle wasting rather than actual fat loss.