Altered Iron Regulation and the Role of Ferritin Heavy Chain in Dermatomyositis Patients

Qingjie Li,1,2,* Xiaoxiao Cheng,1,* Meichen Zhou,1,* Na Ji,1 Sijia Zhu,1 Jianhua Jiang,1 Qi Fang,1 Meirong Liu1 1The Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meirong Liu, First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou, Jiangsu, People’s Republic of China, Tel + 86 18896809225, Email [email protected] Qi Fang, First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou, Jiangsu, People’s Republic of China, Tel + 86 18896809225, Email [email protected]: Dermatomyositis (DM) is an acquired autoimmune disease, the underlying mechanism of which remains unclear. Systemic and myocellular iron homeostasis are deeply connected to inflammation, hypoxia, mitochondrial dysfunction, and different forms of cell death, which are involved in the pathogenesis of DM. This study aimed to investigate changes in key iron regulators transferrin receptor 1(TfR1), ferroportin (Fpn), ferritin heavy chain (FTH), and mitochondrial ferritin (FtMt) in DM and their possible roles.Methods: We included 11 patients with DM, 9 patients with disease controls, and 7 patients as normal controls. Systemically, ELISA was performed to measure the serum hepcidin levels. We used qRT-PCR and Western blotting to quantitatively analyze transferrin receptor 1(TfR1), ferroportin (Fpn), ferritin heavy chain (FTH), and mitochondrial ferritin (FtMt) in the muscle biopsy samples obtained from patients. Immunohistochemical staining and immunofluorescence were performed to determine protein expression.Results: Elevated serum hepcidin levels were observed in the patients with DM. In muscle tissues, the results showed increased mRNA levels of TfR1, Fpn, FTH and elevated protein levels of Fpn, FTH, and FtMt, but not TfR1, indicating an iron-scavenging state in myocytes of DM patients. Ultimately, we observed that FTH enhanced signal intensity was present, especially in perifascicular atrophic myofibers (PFA), but not in necrotic fibers, suggesting a possible role of FTH in PFA.Conclusion: Iron regulators are altered in patients with DM, and the overexpression of FTH may contribute to the pathogenesis of perifascicular atrophy.Keywords: dermatomyositis, iron regulation, ferritin heavy chain, perifascicular atrophy, idiopathic inflammatory myopathy