Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p
Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p
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DOI：
10.1086/507848
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发表时间：
2006-10-01
影响因子：
9.8
通讯作者：
Linne, Maja
中科院分区：
文献类型：
--
作者：
Lee-Kirsch, Min Ae;Gong, Maolian;Linne, Maja
系统性红斑狼疮是一种典型的自身免疫性疾病。除了罕见的补体因子单基因缺陷外，狼疮样疾病可能与其他自身免疫性疾病或细菌感染高度易感性相关，其病因本质上是多因素的。皮肤表现是这种疾病的一个特征，可以单独表现，也可以与内脏疾病相关。我们描述了一种新的遗传性皮肤病，其特征是手指、脚趾、鼻子、脸颊和耳朵等肢端部位疼痛的蓝红色炎性丘疹或结节病变。皮损有时会出现斑块状，并倾向于溃烂。症状通常开始于儿童早期，由寒冷和潮湿的暴露引起。除了关节痛，没有内脏疾病或感染易感性增加的证据。组织学表现包括深部炎性浸润物，分布在血管周围，沿着基底膜有免疫球蛋白和补体的颗粒状沉积。一些受影响的人表现出抗核抗体或免疫复合体形成，而冷球蛋白或冷凝集素缺失。因此，研究结果与冻疮性红斑狼疮是一致的，这是一种罕见的皮肤红斑狼疮。对一个有18个受影响成员的德国大家系的调查表明，这是一个常染色体显性遗传的高渗透性特征。通过基于单核苷酸多态的全基因组连锁分析，将该基因座定位在3p染色体上。单倍型分析将该基因座定义为13.8 cM的间隔，LOD得分为5.04。这是首次描述的单基因形式的皮肤红斑狼疮。家族性冻疮性狼疮的基因鉴定可能有助于揭示系统性红斑狼疮等常见结缔组织疾病的发病机制。
Systemic lupus erythematosus is a prototypic autoimmune disease. Apart from rare monogenic deficiencies of complement factors, where lupuslike disease may occur in association with other autoimmune diseases or high susceptibility to bacterial infections, its etiology is multifactorial in nature. Cutaneous findings are a hallmark of the disease and manifest either alone or in association with internal-organ disease. We describe a novel genodermatosis characterized by painful bluish-red inflammatory papular or nodular lesions in acral locations such as fingers, toes, nose, cheeks, and ears. The lesions sometimes appear plaquelike and tend to ulcerate. Manifestation usually begins in early childhood and is precipitated by cold and wet exposure. Apart from arthralgias, there is no evidence for internal-organ disease or an increased susceptibility to infection. Histological findings include a deep inflammatory infiltrate with perivascular distribution and granular deposits of immunoglobulins and complement along the basement membrane. Some affected individuals show antinuclear antibodies or immune complex formation, whereas cryoglobulins or cold agglutinins are absent. Thus, the findings are consistent with chilblain lupus, a rare form of cutaneous lupus erythematosus. Investigation of a large German kindred with 18 affected members suggests a highly penetrant trait with autosomal dominant inheritance. By single-nucleotide-polymorphism-based genomewide linkage analysis, the locus was mapped to chromosome 3p. Haplotype analysis defined the locus to a 13.8-cM interval with a LOD score of 5.04. This is the first description of a monogenic form of cutaneous lupus erythematosus. Identification of the gene responsible for familial chilblain lupus may shed light on the pathogenesis of common forms of connective-tissue disease such as systemic lupus erythematosus.