关键词: 狼疮性肾炎, 肿瘤坏死因子α诱导蛋白3, A20单倍剂量不足, 自身免疫

Abstract: Ｏｂｊｅｃｔｉｖｅ：To analyze the phenotypic characteristics of patients with lupus nephritis (LN) caused by mutation of TNF-alpha-induced protein 3(TNFAIP3) gene.
Ｍｅｔｈｏｄｏｌｏｇｙ：Clinical and pathological data were collected from 2 LN patients with TNFAIP3 mutations identified through whole-exome sequencing. Validation of the mutations was performed using Sanger sequencing. A comprehensive review of the literature was conducted to summarize the clinical characteristics and pathogenic mutation spectrum.
Ｒｅｓｕｌｔｓ：Patient 1, a female who presented with symptoms at the age of 19, showed kidney involvement characterized by moderate proteinuria and microscopic hematuria. Kidney biopsy indicated LN-Ⅳ+V. Extra-kidney manifestations included recurrent fever, facial erythema, joint pain, hemolytic anemia, and seizures. Whole-exome sequencing revealed a de novo TNFAIP3 gene mutation c.C811T (p.R271*). Patient 2, a male, onset at 29 years, displayed significant proteinuria and microscopic hematuria, with kidney biopsy indicating LN-Ⅳ. Extra-kidney symptoms included rash, hair loss, joint pain, dry mouth, dry eyes, and allergies. His mother had recurrent painless oral ulcers. Whole-exome sequencing identified a TNFAIP3 gene mutation c.634+2T>C (p.D212Gfs*37) inherited from his mother. Literature search found that 14 cases of TNFAIP3 mutation combined with LN were reported, including this study. A total of 13 TNFAIP3 mutations were detected, all of which were heterozygous. Among these patients, females were predominant (12 cases, 85.71％), with onset mostly in childhood; only 2 cases had adult onset. Rash, oral and/or genital ulcers, recurrent fever, and arthritis were the most common extra-kidney manifestations. Ten (71.43％) had multiple autoimmune diseases. The symptoms are effectively controlled after immunosuppressive or biologic treatment in most patients.
Ｃｏｎｃｌｕｓｉｏｎ：LN expression caused by TNFAIP3 gene mutations is complex. For LN patients with multiple autoimmune manifestations, a detailed family history and genetic sequencing should be performed in time to help early diagnosis and personalized treatment.

Key words: lupus nephritis, TNFAIP3, haploinsufficiency of A20, autoimmunity