Chinese scientists have discovered lupus erythematosus caused by a single gene

Systemic lupus erythematosus is a common chronic autoimmune disease with a complex pathogenesis. Chinese scientists have confirmed that defects in the human single gene (PLD4) can lead to systemic lupus erythematosus, providing an important theoretical basis for the precise diagnosis and treatment of systemic lupus erythematosus.

The research team published the research results in the journal Nature on Wednesday (September 10th). Academician Liu Zhihong from Liangzhu Laboratory of Zhejiang University and the National Clinical Research Center for Kidney Diseases, Researcher Yu Xiaomin from Liangzhu Laboratory of Zhejiang University, and Professor Zhou Qing from Liangzhu Laboratory of Zhejiang University and the Institute of Life Sciences of Zhejiang University are the co-corresponding authors of the paper.

It is introduced that Systemic lupus erythematosus is a highly heterogeneous autoimmune disease. There are significant individualized differences both in clinical symptoms and genetic mechanisms. This poses a great challenge to understanding its pathogenesis.

Xinhua News Agency reported that the research team found through whole exome sequencing that five patients with systemic lupus erythematosus nephritis had PLD4 gene mutations. This gene exists in human dendritic cells, B cells and monocytes, and the PLD4 gene mutation is recessive inheritance.

The research team further discovered that this gene mutation triggers the pathogenic mechanism of long-term inflammation and autoimmunity in the body. Through experiments on mice, it was confirmed that certain targeted therapeutic drugs, JAK inhibitors, can significantly alleviate symptoms such as weight loss, autoantibody production, and tissue inflammation in defective mice. This can provide a potential precise treatment strategy for patients with systemic lupus erythematosus carrying the PLD4 mutation. It also provides an important basis for the future development of individualized treatment based on genotyping.