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Objective@#To investigate differentially expressed genes and related signaling pathways in patients with dermatomyositis/clinical amyopathic dermatomyositis (DM/CADM) complicated by interstitial lung disease or malignant tumors.@*Methods@#From January 2017 to January 2018, 27 DM/CADM patients were enrolled from Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and divided into 3 groups according to the complications: 10 with interstitial lung disease, 8 with malignant tumors, and 9 without interstitial lung disease or malignant tumors. Meanwhile, 7 healthy controls were enrolled into this study. High-throughput RNA sequencing was performed to screen differentially expressed genes in peripheral blood in the above 4 groups. Then, these genes were subjected to gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.@*Results@#Compared with the healthy controls, 4 820 up-regulated genes and 137 down-regulated genes were identified in DM/CADM patients; GO analysis revealed 49 significantly enriched items in the DM/CADM patients, 37 (75.5%) of which were associated with biological processes; KEGG analysis showed that differentially expressed genes were mainly enriched in infection-, tumor- and immune-related pathways in DM/CADM patients. Compared with the patients without interstitial lung disease or malignant tumors, 272 up-regulated genes and 158 down-regulated genes were identified in the patients with interstitial lung disease; GO analysis revealed 157 significantly enriched items, 114 (72.6%) of which were associated with biological processes; KEGG analysis showed that differentially expressed genes were mainly enriched in bacterial infection- and autoimmune/inflammatory-related pathways in the patients with interstitial lung disease. Compared with the patients without interstitial lung disease or malignant tumors, 398 up-regulated genes and 68 down-regulated genes were identified in the patients with malignant tumors; GO analysis revealed 117 significantly enriched items, 94 (80.3%) of which were associated with biological processes; KEGG analysis showed that differentially expressed genes were mainly enriched in glycosylation-, metabolism- and tumor-related signaling pathways in the patients with malignant tumors.@*Conclusions@#Differences existed in transcriptomes and pathways between the DM/CADM patients and healthy controls, as well as between the patients with interstitial lung disease or malignant tumors and patients without these complications. Bacterial infection- and cytokine/chemokine-related pathways were significantly enriched in the patients with DM/CADM complicated by interstitial lung disease, while those pathways related to glycosylation, protein metabolism, angtigen presentation and cytotoxic effects of natural killer cells were significantly enriched in the patients with DM/CADM complicated by malignant tumors.
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Objective To investigate differentially expressed genes and related signaling pathways in patients with dermatomyositis/clinical amyopathic dermatomyositis (DM/CADM)complicated by interstitial lung disease or malignant tumors.Methods From January 2017 to January 2018,27 DM/CADM patients were enrolled from Department of Dermatology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,and divided into 3 groups according to the complications:10 with interstitial lung disease,8 with malignant tumors,and 9 without interstitial lung disease or malignant tumors.Meanwhile,7 healthy controls were enrolled into this study.High-throughput RNA sequencing was performed to screen differentially expressed genes in peripheral blood in the above 4 groups.Then,these genes were subjected to gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.Results Compared with the healthy controls,4 820 up-regulated genes and 137 down-regulated genes were identified in DM/CADM patients;GO analysis revealed 49 significantly enriched items in the DM/CADM patients,37 (75.5％) of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in infection-,tumor-and immune-related pathways in DM/CADM patients.Compared with the patients without interstitial lung disease or malignant tumors,272 up-regulated genes and 158 down-regulated genes were identified in the patients with interstitial lung disease;GO analysis revealed 157 significantly enriched items,114 (72.6％)of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in bacterial infection-and autoimmune/inflammatory-related pathways in the patients with interstitial lung disease.Compared with the patients without interstitial lung disease or malignant tumors,398 up-regulated genes and 68 down-regulated genes were identified in the patients with malignant tumors;GO analysis revealed 117 significantly enriched items,94 (80.3％) of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in glycosylation-,metabolism-and tumor-related signaling pathways in the patients with malignant tumors.Conclusions Differences existed in transcriptomes and pathways between the DM/CADM patients and healthy controls,as well as between the patients with interstitial lung disease or malignant tumors and patients without these complications.Bacterial infection-and cytokine/chemokine-related pathways were significantly enriched in the patients with DM/CADM complicated by interstitial lung disease,while those pathways related to glycosylation,protein metabolism,angtigen presentation and cytotoxic effects of natural killer cells were significantly enriched in the patients with DM/CADM complicated by malignant tumors.
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Objective To explore the association of serum cytokine levels with disease activity in patients with dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM),especially their association with skin lesions and interstitial lung disease (ILD).Methods Enzyme-linked immunosorbent assay (ELISA) and cytometric beads array (CBA)were performed to detect the serum levels of interleukin (IL)-2,IL-4,IL-6,IL-10,IL-17A,IL-18,tumor necrosis factor (TNF) and interferon (IFN)-γin 40 patients with DM or CADM,as well as in 16 health checkup examinees (healthy control group).Then,the association of serum cytokine levels with skin lesions,inflammatory biomarkers and severity of ILD was analyzed.Results The patients with DM/CADM showed significantly higher serum levels of IL-6 (37.8 ±45.8 pg/ml),IL-10 (16.1 ± 7.2 pg/ml) and IL-18 (492.0 ± 193.1 pg/ml) compared with the healthy controls (12.0 ± 2.7 pg/ml,7.7 ± 1.4 pg/ml,191.1 ± 39.2 pg/ml,respectively,all P ＜ 0.001),and there were no significant differences in the serum levels of the other 5 cytokines between the above 2 groups.The serum level of IL-6 was significantly higher in patients with elevated erythrocyte sedimentation rate (ESR) than in those with normal ESR (49.7 ± 46.8 pg/ml vs.29.1 ± 45.4 pg/ml,P =0.008).The patients with raised C-reactive protein (CRP) levels showed significantly higher serum levels of IL-6 (68.7 ± 59.7 pg/ml) and IL-18 (635.1 ± 232.8 pg/ml) compared with those with normal CRP levels (IL-6:30.6 ± 40.3 pg/ml,P =0.013;IL-18:440.2 ± 164.7 pg/ml,P =0.020).Moreover,the patients with elevated levels of lactate dehydrogenase (LDH) showed significantly higher serum levels of IL-10 (18.4 ± 6.9 pg/ml),IL-17A (19.6 ±6.7 pg/ml) and IL-18 (529.4 ± 197.2 pg/ml) compared with those with normal LDH levels (IL-10:10.7 ±4.8 pg/ml,P ＜ 0.001;IL-17A:11.4 ± 6.6 pg/ml,P =0.001;IL-18:404.9 ± 158.0 pg/ml,P =0.037).No significant difference in the cytokine levels was observed between the patients with elevated creatine kinase (CK) levels and those with normal CK levels.The patients with Gottron's papules/sign showed significantly higher serum levels of IL-18 (513.7 ± 187.2 pg/ml) compared with those without Gottron's papules/sign (297.1 ± 140.4 pg/ml,P ＜ 0.05).The serum levels of IL-10 and IL-18 were significantly higher in the patients with DM/CADM complicated by ILD (18.0 ± 6.7 pg/ml,552.3 ± 192.8 pg/ml,respectively) than in those without ILD (11.6 ± 6.5 pg/ml,351.4 ± 101.0 pg/ml,respectively,both P =0.001).Conclusion Serum levels of IL-6,IL-10 and IL-18 are highly associated with inflammatory biomarkers,skin lesions and ILD in patients with DM/CADM.