Cryopyrin相关周期性综合征(CAPS)包括一组疾病,其特征是与炎症小体过度激活相关的系统性炎症反复发作。到目前为止,在中国,基因型和表型之间的相关性和治疗策略都没有明确说明。这里,我们研究了中国30例CAPS患者的临床和遗传特征及其相关性。我们通过用ATP加LPS激活外周细胞的NLRP3炎性体确定了新突变的发病机制。将特征与其他案例系列进行比较,并分析了这些患者的治疗结果。患者在NLRP3中有19个替换,其中8个是新的突变。在这些新的突变中,严重骨骼肌肉的百分比,眼科,与其他病例相比,神经系统症状更高。表型及其变异的相关性在我们的案例中似乎有所不同,例如T350M,S333G/I/R,和F311V(躯体镶嵌)。十名患者接受了Canakinumab治疗,被证明能有效缓解骨骼肌肉,神经学,听觉,视觉表现,发烧,和皮疹10-20个月随访。使用泼尼松龙或泼尼松龙联合沙利度胺或甲氨蝶呤治疗的患者,托珠单抗,TNF抑制剂,西罗莫司仅部分缓解。重要的是,我们首先鉴定了F311V的体细胞镶嵌突变,这是严重的。我们的研究扩展了基因型和表型的范围及其相关性的特征,并提供了对不同治疗策略的详细反应。这些数据为CAPS的未来诊断和管理提供了指导。
Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders characterized by recurrent bouts of systemic inflammation related to overactivation of inflammasome. So far, neither large cases of the correlation between genotype and phenotype nor treatment strategies have been clearly stated in China. Here, we studied the clinical and genetic characteristics and their correlation from 30 CAPS patients in China. We identified the pathogenesis for novel mutations by activating NLRP3 inflammasome for peripheral cells with ATP plus LPS, compared characteristics with other case series, and analyzed treatment outcomes of these patients. The patients harbored 19 substitutions in NLRP3, and 8 of them were novel mutations. Among these novel mutations, percentages of severe musculoskeletal, ophthalmologic, and neurological symptoms were higher compared with other case serials. The correlation of phenotypes and their variants seemed different in our cases, such as T350M, S333G/I/R, and F311V (somatic mosaicism). Ten patients received Canakinumab treatment, which proved effective at alleviating musculoskeletal, neurological, auditory, visual manifestations, fever, and rash for 10-20 months follow-up. Patients treated with prednisolone or prednisolone plus thalidomide or methotrexate, tocilizumab, TNF inhibiting agents, and sirolimus achieved only partial remission. Importantly, we firstly identified somatic mosaicism mutation of F311V, which was severe. Our study extended the spectrum of genotype and phenotype and characteristics of their correlations and provided detailed responses to different treatment strategies. These data provide guidance for future diagnosis and management for CAPS.