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To investigate the prevalence and clinical significance of the dense fine speckled (DFS) pattern in a large‐scale cohort of Chinese patients. Data on the antinuclear antibody (ANA) and extractable nuclear antigen (ENA) autoantibody obtained from 165 498 patients who attended Peking Union Medical College Hospital from January 2019 to December 2021 were retrospectively analysed. The prevalence of the DFS pattern was 1.14%, and it mainly appeared in young patients (≤24 years old). A higher positive rate of the DFS pattern was observed in patients with dermatosis (18.12%) and systemic autoimmune rheumatic diseases (SARDs) (13.53%). The DFS pattern titre was mostly low or medium (≤1:160). A higher titre was associated with an increased risk of SARDs (p <.001), dermatosis (p =.015) and pulmonary disease (p =.016). In 37 patients with ENA autoantibody positivity, anti‐SSA antibody was the most common (2.55%). If the low titre (<1:160) or the DFS pattern with negative ENA autoantibody were to be used as exclusion criteria for SARDs, the diagnosis would have been missed in 42 or 77 patients, respectively. The prevalence of the DFS pattern was low in ANA test samples and was more common in patients with dermatosis and SARDs, but the titre was usually higher in patients with SARDs. There was no evidence that the DFS pattern could be used as an exclusion criterion for SARDs diagnosis. The DFS pattern was associated with certain pathological states, which may inform the clinical significance of the DFS pattern. [ABSTRACT FROM AUTHOR]

• miR-181d-5p expression was downregulated in PBMCs of LN patients and MRL/lpr mice. • miR-181d-5p can directly target binding to MAPK8. • Overexpression of miR-181d-5p inhibited the phosphorylation of p38 and p44/42 in the THP-1 cells. • Overexpression of miR-181d-5p elevated THP-1 cell viability and decreased the inflammatory response. • Overexpression of miR-181d-5p decreased antinuclear antibodies and fibrosis levels in MRL/lpr mice. Lupus nephritis (LN) is a common immune disease. The microRNA (miR)-181d-5p is a potential target for treating kidney injury. However, the therapeutic role of miR-181d-5p in LN has not been investigated. This study aimed to investigate the role of miR-181d-5p in targeting mitogen-activated protein kinase 8 (MAPK8) and stimulating the MAPK signaling pathway in LN. RT-qPCR was performed to identify the variations in miR-181d-5p expression in peripheral blood mononuclear cells (PBMCs) obtained from 42 LN patients, 30 healthy individuals, 6 MRL/lpr mice and 6 C57BL/6 mice. Western blot was used to detect the effect of miR-181d-5p on the MAPK signaling pathway in THP-1 cells and MRL/lpr mice. Enzyme-linked immunosorbent assay (ELISA) was utilized to detect the effect of miR-181d-5p on antinuclear antibodies and inflammatory factors. A dual-luciferase reporter assay was used to verify whether miR-181d-5p directly targets MAPK8. Flow cytometry was performed to evaluate apoptosis rates in transfected THP-1 cells. miR-181d-5p expression was downregulated in PBMCs of LN patients (P < 0.01) and MRL/lpr mice (P < 0.05). A dual luciferase reporter assay demonstrated that miR-181d-5p inhibits MAPK8 (P < 0.01). Overexpression of miR-181d-5p inhibited the phosphorylation of p38 (P < 0.001) and p44/42 (P < 0.01). Moreover, miR-181d-5p decreased the apoptosis rate of THP-1 cells (P < 0.001), and reduced the secretion of IL-6 (P < 0.01) and TNF-α (P < 0.01). Furthermore, overexpression of miR-181d-5p decreased anti-dsDNA antibody (P < 0.05), anti-Sm antibody (P < 0.01), and fibrosis levels in MRL/lpr mice. Upregulation of miR-181d-5p showed anti-inflammatory and anti-apoptotic effects on THP-1 cells in vitro and kidney injury in vivo. These effects were achieved by miR-181d-5p targeting MAPK8 to inhibit phosphorylation of p38 and p44/42. These results may offer new insights for improving therapeutic strategies against lupus nephritis. [ABSTRACT FROM AUTHOR]