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This study aimed to evaluate the relative risk of malignancy in patients with Takayasu's arteritis compared to that in the general population. This retrospective nationwide cohort study used data from the Korean Health Insurance Review and Assessment Service database. All newly diagnosed patients with Takayasu's arteritis were identified between January 2009 and December 2019. They were observed until the diagnosis of malignancy, death, or end of the observational period, December 2020. The standardized incidence ratios (SIRs) of the overall and site-specific malignancies were estimated and compared with the incidence of cancer in the general population retrieved from the National Cancer Registry. We identified 1449 newly diagnosed patients with Takayasu's arteritis during the observational period (9196 person-years). A total of 74, 66, and 8 patients had overall, solid, and hematologic malignancies, respectively. The risks of overall [SIR, 1.62; 95% confidence interval (CI) 1.27–2.03], solid (SIR, 1.51; 95% CI 1.17–1.92), and hematologic (SIR, 4.05; 95% CI 1.75–7.98) malignancies were increased compared to those in the general population. In solid malignancies, breast (SIR, 2.07; 95% CI 1.16–3.42) and ovarian (SIR, 4.45; 95% CI 1.21–11.39) cancers had an increased risk. In hematologic malignancies, the risk of myelodysplasia increased (SIR, 18.02; 95% CI 3.72–52.66). Immunosuppressive agent use was not associated with malignancy. There was no specific period when cancer more frequently occurred. An increased risk of malignancy was observed in patients with Takayasu's arteritis compared to that in the general population in this large-scale nationwide population study of Korean health insurance data. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the effect of α-defensin-1 on the expression of IL-6, IL-8 and MMPs as well as the signal transduction mechanisms responsible for their expression in RA fibroblast-like synoviocytes (FLS).Methods. The concentrations of α-defensin-1 in SF were measured by ELISA. In RA FLS, mRNA expression of IL-6, IL-8 and MMPs and activation of signalling molecules were examined by real-time PCR, western blotting and electrophoretic mobility shift assay.Results. Concentrations of SF α-defensin-1 were significantly increased in RA patients compared with OA patients. The levels of mRNA expression of IL-6, IL-8, MMP-1 and MMP-3 were significantly increased in RA FLS treated with α-defensin-1 compared with controls. Furthermore, α-defensin-1 activated JNK and ERK in RA FLS, respectively. Treatment of RA FLS with ERK or JNK inhibitors prior to α-defensin-1 treatment resulted in reduced expression of IL-6, IL-8, MMP-1, and MMP-3 compared with controls. Remarkably, treatment of RA FLS with an ERK inhibitor prior to α-defensin-1 stimulation significantly reduced production of IL-6 and MMP-1 by approximately 71% and 98% compared with controls, respectively. The JNK inhibitor significantly suppressed α-defensin-1-induced MMP-1 production by approximately 73% compared with controls. Finally, there was a significant induction of NF-κB DNA binding activity in response to α-defensin-1.Conclusion. Our results suggest that α-defensin-1 may play a role in RA pathogenesis by regulating the production of MMPs as well as IL-6 and IL-8. These processes were dependent on the regulation of the JNK and/or ERK and NF-κB pathways. [ABSTRACT FROM PUBLISHER]