Familial Chilblain Lupus Due to a Novel Mutation in the Exonuclease III Domain of 3' Repair Exonuclease 1 (TREX1)
Familial Chilblain Lupus Due to a Novel Mutation in the Exonuclease III Domain of 3' Repair Exonuclease 1 (TREX1)
复制标题
DOI：
10.1001/jamadermatol.2014.3438
复制
发表时间：
2015-04-01
期刊：
影响因子：
10.9
通讯作者：
Lee-Kirsch, Min Ae
中科院分区：
文献类型：
--
作者：
Guenther, Claudia;Berndt, Nicole;Lee-Kirsch, Min Ae
家族性冻疮性狼疮是一种罕见的常染色体显性遗传型红斑狼疮，其特征是在儿童早期出现肢端部位的冷诱导炎性病变。家族性冻疮狼疮通常是由TREX 1（3'修复核酸外切酶1）突变引起的。585 C>G; H195 Q）。受影响的家庭成员经历了不同程度的冷诱导冻疮病变，从蓝红色浸润到致残性坏死性溃疡。此外，所有患者均表现出全身性疾病的体征，如关节炎、淋巴细胞减少症或抗核抗体。一个增加的表达ofmyxovirus抗性蛋白A在皮肤和外周血细胞中的干扰素刺激的基因的诱导表明激活I型interferon.CONCLUSIONS和RELEVANCE这种情况下，进一步牵连I型干扰素依赖性先天免疫激活TREX 1相关的家族性冻疮狼疮的发病机制。与以前报道的TREX 1突变，影响Exo I或Exo II结构域不同，这里提出的突变改变了Exo III结构域，表明在家族性冻疮狼疮的发病机制中，催化性Exo结构域内的突变具有特定的作用。高患病率的皮外表现，沿着激活的I型干扰素，强调了家族性冻疮狼疮的系统性。
IMPORTANCE Familial chilblain lupus is a rare, autosomal dominant form of lupus erythematosus characterized by cold-induced inflammatory lesions at acral locations presenting in early childhood. Familial chilblain lupus is usually caused by a mutation in TREX1 (3' repair exonuclease 1).OBSERVATIONS We report on a family with dominant chilblain lupus segregating a novel TREX1 mutation (c. 585C>G; H195Q) within the highly conserved exonuclease (Exo) III domain. Affected family members experienced cold-induced chilblain lesions of varying degrees, ranging from bluish-red infiltrations to mutilating necrotic ulcerations. In addition, all patients showed signs of systemic disease, such as arthritis, lymphopenia, or antinuclear antibodies. An increased expression ofmyxovirus resistance protein A in the skin and induction of interferon-stimulated genes in peripheral blood cells demonstrated activation of type I interferon.CONCLUSIONS AND RELEVANCE This case further implicates type I interferon-dependent innate immune activation in the pathogenesis of TREX1-associated familial chilblain lupus. Unlike previously reported TREX1 mutations, which affect the Exo I or Exo II domains, the mutation presented here alters the Exo III domain, suggesting a particular role of mutations within the catalytic Exo domains in the pathogenesis of familial chilblain lupus. The high prevalence of extracutaneous manifestations, along with activation of type I interferon, underlines the systemic nature of familial chilblain lupus.