Genetic association of cutaneous neonatal lupus with HLA class II and tumor necrosis factor α
Genetic association of cutaneous neonatal lupus with HLA class II and tumor necrosis factor α
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DOI：
10.1002/art.20442
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发表时间：
2004-08-01
影响因子：
--
通讯作者：
Buyon, JP
中科院分区：
文献类型：
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作者：
Clancy, RM;Backer, CB;Buyon, JP
Objective.皮肤新生儿狼疮类似于亚急性皮肤红斑狼疮（SCLE），光敏性是一种常见的症状。暴露于紫外线的角质形成细胞释放的肿瘤坏死因子α（TNF α）可能在具有单倍型TNF α-308A的DRB 1 *03的SCLE患者中被夸大。因此，本研究旨在寻找TNF α在新生儿皮肤狼疮发病机制中作用的遗传学和组织学证据。从新生儿狼疮研究登记处的83名儿童（22名皮疹，35名先天性心脏传导阻滞[CHB]，26名未受影响的兄弟姐妹）和58名母亲中分离DNA。-308A等位基因（与较高的TNF α产生相关）、HLA-DRQB 1 *02和HLA-DRB 1 *03分别存在于大多数皮疹儿童中（分别为64%、68%和64%）。所有3个6p等位基因同时出现在一个个体中的频率在皮疹患儿中高于CHB或无新生儿狼疮表现的患儿（59%对30%; P = 0.02）。这种与新生儿狼疮性皮疹的相关性与发表的SCLE患者队列的结果相当，但显著高于盘状红斑狼疮患者的相关性。3例皮疹患儿皮损表皮中TNF α染色明显，而健康儿童皮损表皮中TNF α染色不明显。总之，发现组织损伤后TNF α水平升高的遗传倾向和靶器官中TNF α的组织学表现支持这种炎性细胞因子在皮肤新生儿狼疮发病机制中起作用的观点。此外，这些研究的结果提供了新生儿狼疮和SCLE皮疹之间存在生物学联系的证据。
Objective. Cutaneous neonatal lupus resembles subacute cutaneous lupus erythematosus (SCLE), and photosensitivity is a common symptom. Tumor necrosis factor alpha (TNFalpha) release by ultraviolet light-exposed keratinocytes may be exaggerated in SCLE patients who have the haplotype TNFalpha -308A;DRB1*03. Accordingly, this study was undertaken to seek genetic and histologic evidence for a role of TNFalpha in the pathogenesis of cutaneous neonatal lupus.Methods. DNA was isolated from 83 children (22 with rash, 35 with congenital heart block [CHB], 26 unaffected siblings) and 58 mothers from the Research Registry for Neonatal Lupus.Results. The -308A allele (associated with higher TNFalpha production), HLA-DRQB1*02, and HLA-DRB1*03 were each present in the majority of children with rash (64%, 68%, and 64%, respectively). The frequency of all 3 6p alleles occurring together in 1 individual was greater in children with rash than in children who had either CHB or no manifestation of neonatal lupus (59% versus 30%; P = 0.02). This association with neonatal lupus rash was equivalent to published findings in a cohort of patients with SCLE, but significantly greater than the association in patients with discoid lupus erythematosus. Prominent TNFalpha staining in the epidermis was observed in lesional skin from 3 children with rash, but not in skin from a healthy neonate.Conclusion. Taken together, the finding of a genetic predisposition to generate increased levels of TNFalpha following tissue injury and the histologic demonstration of TNFalpha in the target organ support the notion that this inflammatory cytokine plays a role in the pathogenesis of cutaneous neonatal lupus. Furthermore, the results of these studies provide evidence of a biologic link between neonatal lupus and the rash of SCLE.