Serum RIPK3/MLKL as exploratory biomarker candidates for systemic lupus erythematosus

Objective This study aims to elucidate the novel role of serum receptor interacting protein kinase 3 (RIPK3)/mixed series of protein kinase-like domains (MLKL) levels in SLE and assess their correlation with clinical manifestations and serological parameters. Methods We employed enzyme-linked immune sorbent assay (ELISA) analysis to evaluate RIPK3/MLKL protein levels in serum from 90 SLE patients and 50 healthy controls (HC). Results Our findings reveal a significant elevation of serum RIPK3/MLKL protein levels in SLE patients compared to HC ( p = 0.0004 and p = 0.0005, respectively). Notably, these levels were closely associated with the disease’s clinical manifestations, notably heightened in active SLE compared to stable cases ( p = 0.0312 and p = 0.0096, respectively). Furthermore, while RIPK3 protein exhibited significant upregulation in patients with lupus nephritis (LN) compared to non-LN individuals ( p = 0.0017). SLE patients with high anti-nuclear antibody (ANA) titers exhibited notably higher RIPK3 levels compared to those with low ANA titers ( p < 0.0001). The receiver operating characteristic (ROC) curve demonstrated diagnostic potential for serum RIPK3/MLKL, with respective areas under the curve (AUCs) of 0.6319 ( p = 0.0099) and 0.7374 ( p < 0.0001). Conclusions Our study illuminate serum RIPK3/MLKL proteins are exploratory biomarker candidates for SLE and necroptosis may be involved in SLE pathogenesis.