New research connects the dots between immune activation, cardiovascular dysfunction and muscle recovery in this rare paediatric autoimmune disease.
Emerging research continues to underscore the central role of neutrophil activation in the pathogenesis and clinical progression of juvenile dermatomyositis (JDM), revealing complex links between inflammation, muscle damage and vascular dysfunction.
The first study, presented at an ACR paediatric rheumatology session has identified a potential mechanistic link between neutrophil activation, HDL dysfunction and early atherosclerosis in juvenile dermatomyositis (JDM), offering novel insights into the cardiovascular implications of this rare autoimmune condition.
While adults with dermatomyositis face a well-documented two- to threefold increased risk of major adverse cardiovascular events due to systemic inflammation, endothelial injury and metabolic complications, the cardiovascular burden in children with JDM has remained largely undefined, the researchers said.
The current findings suggest that similar, and perhaps even earlier, vascular pathology may be at play in paediatric disease.
The University of Michigan researchers evaluated cholesterol efflux capacity (CEC), a key functional property of HDL that reflects its ability to remove cholesterol from macrophages, in plasma from 51 children with JDM compared with 24 paediatric controls.
They also measured paraoxonase-1 (PON1) activity, an antioxidant enzyme associated with HDL integrity and cardiovascular protection and assessed fatty acid uptake in a foam cell assay to determine the pro-atherogenic potential of circulating lipoproteins.
JDM patients showed significantly impaired CEC and lower PON1 activity compared with controls, consistent with dysfunctional HDL.
“CEC was inversely correlated with fatty acid uptake in a foam cell assay (r = –0.39, p = 0.0045), indicating a shift toward a more pro-atherogenic state marked by increased lipid accumulation in macrophages,” the researchers reported.
“Among JDM patients, those with elevated circulating calprotectin had significantly lower CEC and PON1 activity, linking neutrophil activation and NET-associated inflammation to HDL dysfunction.”
In a separate study, also out of the US but this time from the University of Washington, researchers investigated the clinical utility of neutrophil activation markers, specifically calprotectin (S100A8/A9) and myeloperoxidase (MPO)-DNA complexes, as potential biomarkers for muscle inflammation and predictors of muscle outcomes in JDM.
Their findings were published this month in Paediatric Rheumatology, and highlighted the potential of neutrophil activation markers as indicators of disease activity and muscle recovery in JDM, offering a promising step toward improved disease monitoring and individualised treatment in paediatric rheumatology
The researchers examined plasma levels of calprotectin and myeloperoxidase (MPO)-DNA complexes in 36 children with JDM, 13 with juvenile idiopathic arthritis (JIA) and 21 healthy controls.
They found that both markers were significantly elevated in JDM compared with healthy participants, confirming heightened neutrophil activation in affected patients. Elevated calprotectin and MPO-DNA levels were associated with greater muscle inflammation and poorer muscle function, as assessed by the Childhood Myositis Assessment Scale (CMAS), Physician Global Assessment (PGA) and Manual Muscle Testing (MMT8).
“ROC curve analysis suggested that neutrophil activation markers may have better diagnostic performance than CK in distinguishing active disease,” the researchers wrote.
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“However, these markers reflect different biological processes from CK and are therefore more likely to serve as complementary tools rather than replacements.
“Stratification by neutrophil biomarker levels revealed significant differences in baseline muscle involvement, laying the groundwork for improved assessment and individualised treatment. Larger studies are needed to validate these findings and explore their predictive value.”
Notably, patients with simultaneous elevations in both calprotectin and MPO-DNA displayed more pronounced muscle involvement, indicating that dual biomarker assessment may help identify those with more severe disease.
Longitudinal analysis further revealed that higher baseline levels of these neutrophil activation markers were linked to greater improvement in muscle strength over time, suggesting a potential role in predicting treatment response and recovery trajectories.
Although the study cohort was modest in size, the researchers said their findings pointed to a complex, dual role for neutrophils in JDM pathogenesis – exacerbating tissue injury during active inflammation but possibly contributing to muscle repair during recovery.
“Similar associations have been noted in rheumatoid arthritis (RA), where elevated baseline neutrophil elastase (NE)–DNA and calprotectin predict better treatment responses,” they wrote.
“However, it is also possible that patients with higher baseline neutrophil activation had more severe disease at presentation and consequently received more intensive immunosuppressive therapy, resulting in greater improvement over time.
“Thus, the observed association may be at least partially confounded by differences in treatment intensity or approach. Further studies with larger cohorts and detailed treatment data are needed to disentangle the effects of disease severity, treatment, and neutrophil activation on muscle outcomes in JDM.”
ACR Convergence 2025 was held in Chicago from 24-29 October.
