Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra
Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra
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DOI：
10.1002/art.20033
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发表时间：
2004-02-01
影响因子：
--
通讯作者：
McDermott, MF
中科院分区：
文献类型：
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作者：
Hawkins, PN;Lachmann, HJ;McDermott, MF
客观的。 NALP3/CIAS1/PYPAF1 基因突变与自身炎症性疾病 Muckle-Wells 综合征 (MWS)、家族性寒冷性自身炎症综合征 (FCAS) 和新生儿发病的多系统炎症性疾病 (NOMID) 相关，后者也称为慢性婴儿神经、皮肤、关节 (CINCA) 综合征。分子研究表明 NALP3 参与白细胞介素 1 β (IL-1 β) 的加工，促使我们研究 IL-1 阻断是否可能对 MWS 患者具有治疗作用。方法。我们回顾了一个家庭 3 名成员的临床特征，他们都患有与 NALP3 变体 V200M（也称为 V198M）相关的 MWS，并评估了他们的炎症性疾病对重组人 IL-1 受体拮抗剂阿那白滞素治疗的反应。受试者记录症状日记并每两周接受一次临床和实验室评估，包括测量血清淀粉样蛋白 A 浓度。结果。每个受试者都有发烧、皮疹、关节痛、结膜炎、感音神经性耳聋和 MWS 特征的强烈急性期反应。然而，还发现了其他特征，包括寒冷和神经系统表现导致疾病恶化，这些特征迄今为止仅在 FCAS 和 NOMID 中分别描述过。在阿那白滞素治疗期间，活动性炎症性疾病的临床和血清学证据迅速且完全消退。结论。 MWS 对阿那白滞素的显着反应表明 IL-1β 在与 NALP3 基因突变相关的炎症发病机制中具有重要作用，并支持在 NOMID/CINCA 综合征或 FCAS 患者中抑制 IL-1 的研究。与 NALP3 基因突变相关的各种综合征的临床特征可能比以前认识到的更大程度重叠。
Objective. Mutations in the NALP3/CIAS1/ PYPAF1 gene are associated with the autoinflammatory diseases Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal-onset multisystem inflammatory disease (NOMID), which is also known as chronic infantile neurologic, cutaneous, articular (CINCA) syndrome. Molecular studies suggest that NALP3 is involved in the processing of interleukin-1beta (IL-1beta), prompting us to investigate whether IL-1 blockade may be therapeutic in patients with MWS.Methods. We reviewed the clinical features of 3 members of a family, all of whom had MWS associated with the NALP3 variant V200M (also designated V198M), and evaluated the response of their inflammatory disease to treatment with the recombinant human IL-1 receptor antagonist anakinra. The subjects kept a diary of symptoms and underwent fortnightly clinical and laboratory assessments, including measurement of the serum amyloid A protein concentration.Results. Each subject had fever, rashes, arthralgia, conjunctivitis, sensorineural deafness, and an intense acute-phase response characteristic of MWS. However, additional features were identified, including exacerbation of their disease by cold and neurologic manifestations, that have hitherto been described only in FCAS and NOMID, respectively. Clinical and sero logic evidence of active inflammatory disease resolved rapidly and completely during treatment with anakinra.Conclusion. The remarkable response of MWS to anakinra suggests that IL-1beta has a fundamental role in the pathogenesis of inflammation associated with mutations in the NALP3 gene, and supports study of IL-1 inhibition in patients with NOMID/CINCA syndrome or FCAS. The clinical features of the various syndromes associated with mutations in the NALP3 gene may overlap to a greater extent than has previously been recognized.