Distinct cytokine signature in juvenile dermatomyositis: linking myositis-specific antibodies and clinical manifestations.
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OBJECTIVES: Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune inflammatory myopathy characterized by muscle and skin involvement. Myositis-specific autoantibodies (MSAs) define distinct clinical subgroups, yet the underlying inflammatory mechanisms remain unclear. This study aimed to investigate serum cytokine profiles in patients with JDM and their associations with MSA subgroups, clinical features, and laboratory findings. METHODS: Serum levels of interferon (IFN)-α, interleukin (IL)-18, C-X-C motif chemokine ligand 9 (CXCL9), soluble tumor necrosis factor receptor type II (sTNF-RII), and IL-6 were measured in patients with JDM using enzyme-linked immunosorbent assays. Results were compared with clinical symptoms and laboratory parameters in each MSA subgroup. To explore cytokine-based disease classification, principal component analysis (PCA) and hierarchical clustering were performed. RESULTS: Serum cytokine profiles differed across MSA subgroups. Patients with anti-melanoma differentiation-associated protein 5 (MDA5) antibodies exhibited significantly elevated IFN-α, IL-18, and CXCL9 levels, correlating with lung involvement. Patients with anti-nuclear matrix protein 2 (NXP2) antibodies demonstrated increased sTNF-RII and IL-6 levels, which were strongly associated with muscle injury markers. Patients with anti-transcriptional intermediary factor 1 gamma (TIF1γ) antibodies exhibited slight increase in cytokine levels, suggesting a different inflammatory pathway. PCA and clustering analysis further supported the cytokine-based classification of JDM. CONCLUSIONS: Distinct cytokine signatures in the JDM subgroups underscore their role in disease heterogeneity and clinical presentation. These findings support cytokine profiling as a potential tool for patient classification and personalized treatment.