LSO-056 Impaired function of neutrophil cytosolic factor 2 (NCF2) may participates in lupus from multiple pathways

Background

Systemic lupus erythematosus (SLE) is a complex autoimmune and hereditary disease. We found that the mutation rs13306575 located in NCF2 is associated with the lupus phenotype, and we aim to explore its relationship with SLE.

Methods

Transcriptome analysis was performed using public databases on the transcriptome of various tissues in lupus. Blood samples were collected and qPCR was used to verify the expression of NCF2 in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls (HC). The rs13306575 mutant (NCF2 R395W mutation) cell lines of NCF2 was constructed. Co-immunoprecipitation was used to observe the binding of NCF2 to its ligand. The effects of NCF2 on inflammation were detected by fluorescence microscopy, ELISA, Western Blot and qPCR.

Results

NCF2 expression was decreased in PBMCs and lupus nephritis kidneys in SLE patients compared with HC. Similar to NCF2-cells, NCF2 R395W mutation reduced the function of NADPH oxidase and the ability to produce reactive oxygen species (ROS). Meanwhile, the mutation reduced the binding of NCF2 to NCF4. Under different stimuli, NCF2- and mutant cells showed decreased expression of NETs and altered expression of p38MAPK signaling pathway to varying degrees.

Conclusions

In conclusion, the missense mutation rs13306575 lead to decreased expression of NCF2 and declined function of NADPH oxidase, which may be involved in SLE through multiple mechanisms.