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Abstract Background Little is known about the features of macrophage activation syndrome (MAS) in dermatomyositis, especially the association between rapidly progressive interstitial lung disease (RP‐ILD) and MAS. Objective To determine the characteristics of MAS in patients with dermatomyositis and their association with RP‐ILD. Methods This was a retrospective cohort study of 201 dermatomyositis patients at the First Affiliated Hospital of Zhejiang University over a 10‐year period. Results A total of 22 (10.9%) patients were diagnosed with MAS. The rate of RP‐ILD was significantly higher in patients with MAS than in those without MAS (81.8% vs. 17.4%, respectively, p 1685 ng/mL (p = .007) and hemoglobin

Objective. Iguratimod, a novel disease-modifying anti-rheumatic drug for the treatment of rheumatoid arthritis, has been approved in China and Japan. Here, we aimed to find whether iguratimod can inhibit the aggressive behavior and promote apoptosis of rheumatoid fibroblast-like synoviocytes (RA-FLSs). Methods. The proliferation of RA-FLSs was assessed by 5-ethynyl-2′-deoxyuridine test and Cell Counting Kit-8. Migration and invasion were determined by the wound test and a transwell assay. Apoptosis was tested by flow cytometry. The mRNA expression of matrix metalloproteinases (MMPs) and proinflammatory cytokines in RA-FLSs were measured by quantitative PCR and ELISA. To gain insight into the molecular signaling mechanisms, we determined the effect of iguratimod on the activation of mitogen-activated protein kinases (MAPK) signaling pathways by the cellular thermal shift assay (CETSA) and western blot. Results. Iguratimod treatment significantly reduced the proliferation, migration, and invasive capacities of RA-FLSs in a dose-dependent manner in vitro. MMP-1, MMP-3, MMP-9, Interleukin-6 (IL-6), and monocyte chemoattractant protein-1 mRNA and protein levels were all decreased after treatment with iguratimod. Furthermore, tumor necrosis factor-alpha- (TNF-α-) induced expression of phosphorylated c-Jun N-terminal kinases (JNK) and P38 MAPK were inhibited by iguratimod. Additionally, iguratimod promoted the apoptosis of RA-FLSs. Most importantly, iguratimod was shown to directly interact with JNK and P38 protein by CETSA assay. Moreover, activating transcription factor 2 (ATF-2), a substrate of both JNK and P38, was suppressed by iguratimod. Conclusions. Our findings suggested that the therapeutic effects of iguratimod on RA might be, in part, due to targeting the aggressive behavior and apoptosis of RA-FLSs.

The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren’s syndrome (pSS). The inhibitor of κB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ε in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε (pIKKε), pIκBα, and pNF-κB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/β and pIKKγ were both negative. And pIKKε positively related to expression of p-p65. Furthermore, pIKKε and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγ and IκBα between pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKε expression and deregulation of NF-κB pathway.