关键词: 葡萄糖6磷酸脱氢酶, 系统性红斑, 狼疮狼疮性, 肾炎溶血性贫血

Abstract: Ｏｂｊｅｃｔｉｖｅ：To summarize the clinical and pathological characteristics of 3 patients with lupus nephritis who carried the missense variants of glucose 6-phosphate dehydrogenase (G6PD) and to discuss the clinical value of G6PD variants detection in systemic lupus erythematosus.
Ｍｅｔｈｏｄｏｌｏｇｙ：We collected the clinical and pathological data of 3 patients with lupus nephritis in Jinling Hospital. Pathogenic variants was screened by whole-exome sequencing (WES) in the patients and validated by Sanger sequencing in family members. G6PD／6PGD ratio method was used to test the G6PD enzyme activity. Quantitative polymerase chain reaction (qPCR) and cytometric bead array (CBA) was used to detect inflammatory signatures in two patients.
Ｒｅｓｕｌｔｓ：All the 3 patients had a history of pancytopenia. Coombs tests were negative, but the red blood cell fragments were all positive. WES identified two kinds of variants in G6PD gene. Two males had a hemizygous variant of c.G1466T (p.R489L) inherited from their mother, while the female patient had a compound heterozygous variant of c.G1466T (p.R489L) and c.G1478A (p.R493H) inherited from the parents. The G6PD enzyme activity were all deficient. We further identified hyperactivation signatures of type I interferon signaling and overproduction of pro-inflammatory cytokines in the blood of two patients. Compared with the normal controls, the expression of in terferon-stimulated genes IFIT1, IFI44L, OAS1 and MX2 in blood cells of two patients was significantly higher, as well as the serum IL-8 and IP-10 levels.
Ｃｏｎｃｌｕｓｉｏｎ：Lupus nephritis patients with G6PD gene variants may present with anemia as the first or prominent clinical manifestation, accompanied by excessive activation of type I interferon signal pathway and excessive production of inflammatory cytokines in the blood. Its role in the pathogenesis of SLE deserves further study.

Key words: glucose 6-phosphate dehydrogenase variants, systemic lupus erythematosus, lupus nephritishemolytic anemia