关键词: 狼疮肾炎, KRAS, 致病变异, 自身免疫

Abstract: Objective:To investigate the phenotypic and genotypic characteristics of lupus nephritis (LN) patients with KRAS mutations. Methods:Clinical and pathological data were collected from LN patients carrying pathogenic KRAS variants identified by whole-exome sequencing or whole-genome sequencing.Genetic profiles,clinical manifestations,renal pathology and treatment outcomes were integrated for analysis. Results:Five LN patients with heterozygous pathogenic KRAS mutations were identified,involving 4 distinct variants:3 missense (G13D,V114A,A146V) and one in-frame deletion (E175del). All patients had notable hematologic abnormalities, including pancytopenia (n=5) and persistent monocytosis (n=2):3 paients preented with splenomegaly or lymphadenopathy. Renal pathology was highly heterogeneous,ranging from mild mesangial lesions to severe diffuse proliferative glomerulonephritis with crescent formation. Treatment mainly involved glucocorticoids combined with immunosuppressants;4 patients achieved complete or partial remission,while one showed poor response and progressed to end-stage renal disease. Conclusion:LN patients with KRAS variants present a subset of distinct clinical phenotypes.Genetic screening in individuals with early-onset disease (in some cases) or prominent hematologic abnormalities may help identify underlying genetic causes and inform potential therapies targeting Ras-MAPK pathway.

Key words: lupus nephritis,KRAS,pathogenic variant,autoimmunity