Monocyte human leukocyte antigen-DR-mediated diabetic nephropathy progression is a promising therapeutic target.

Objective: Increasing evidence has suggested that immune cells are known to play a pivotal role in the progression of diabetic nephropathy (DN). However, the specific causal role of monocyte surface markers, particularly human leukocyte antigen-DR (HLA-DR), remains unclear. This study aims to investigate the causal relationship between monocyte HLA-DR expression and DN risk and to validate its clinical relevance. Methods: We first employed a detailed two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationships involving immune cell signatures particularly monocytes and DN risk. Then, to clinically validate these findings, we used flow cytometry to detect the median fluorescence intensity (MFI) of HLA-DR on monocyte in peripheral blood from DN patients and normal controls and analyzed its correlation with key renal function indicators of DN patients. Results: Two monocyte-related immune cell signatures were identified significantly associated with DN risk via MR analyses after false discovery rate (FDR) correction: Conclusions: Our findings demonstrate that the elevated MFI of HLA-DR