HANGZHOU -- A recent study led by Chinese scientists has identified a gene defect -- PLD4 deficiency -- that can cause systemic lupus erythematosus (SLE), a chronic and complex autoimmune disease affecting millions of patients worldwide. The findings, published in Nature on Wednesday, provide crucial insights for future targeted therapies.

The research was conducted by a team from Liangzhu Laboratory at Zhejiang University, with Liu Zhihong, Yu Xiaomin, and Zhou Qing as co-corresponding authors.

SLE is characterized by high heterogeneity, varying widely in both clinical manifestations and genetic background, which has long complicated understanding of its pathogenesis.

Using whole-exome sequencing, the team identified recessive mutations in the PLD4 gene in five SLE patients with lupus nephritis. The PLD4 gene is expressed in key immune cells, including dendritic cells, B cells, and monocytes. The deficiency of PLD4 was shown to trigger sustained inflammation and autoimmune activation.

Further validation in mouse models demonstrated that baricitinib, a JAK inhibitor, effectively alleviated symptoms such as weight loss, autoantibody production, and tissue inflammation in mice with the PLD4 defect.

This breakthrough suggests that baricitinib may offer a targeted therapy for SLE patients with PLD4 mutations, paving the way for genotype-based personalized medicine in lupus care.