NLRP12-associated autoinflammatory disease: A novel causal mutation and bioinformatics analyses

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Zhonghua Li , Qi Zhi , Jiahuang Li , Bo Zhu
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Abstract

Nucleotide-binding leucine-rich repeat-containing receptor 12-associated autoinflammatory disease (NLRP12-AID) is a rare autosomal dominant disorder. In this study, we reported a case of this rare disease with a novel NLRP12 mutation (A218V, rs749659859). The patient displayed typical symptoms, including recurrent fever, arthralgia, and skin allergies. Elevated serum IgE, decreased apolipoprotein A1, high-density lipoprotein cholesterol, and fluctuating levels of various leukocyte subtypes, procalcitonin, IL6, creatine kinase, and 25-hydroxyvitamin D were also detected. Inflammatory lesions were observed in multiple organs using 18F-FDG PET/CT. By mining single-cell transcriptome data, we identified relatively high expression of NLRP12 in monocytes compared to other human peripheral blood mononuclear cells. NLRP12-positive monocytes exhibited reduced expression of IL18, CCL3, and TNFA compared to NLRP12-negative monocytes. Structural analyses suggested that the A218V mutation, along with A218T and F402L, may reduce the ATP-binding affinity of the NLRP12 protein. These findings may provide new insights into the mechanisms of NLRP12-AID, and suggest the potential ATP-based therapy for further investigation.

NLRP12相关自身炎症性疾病:一种新的致病突变和生物信息学分析
核苷酸结合富亮氨酸重复受体 12 相关自身炎症性疾病(NLRP12-AID)是一种罕见的常染色体显性遗传疾病。在这项研究中,我们报告了一例患有新型 NLRP12 基因突变(A218V,rs749659859)的罕见病例。患者表现出典型症状,包括反复发热、关节痛和皮肤过敏。血清 IgE 升高,脂蛋白 A1 和高密度脂蛋白胆固醇降低,各种白细胞亚型、降钙素原、IL6、肌酸激酶和 25- 羟维生素 D 水平波动。使用18F-FDG PET/CT在多个器官中观察到炎症病变。通过挖掘单细胞转录组数据,我们发现与其他人类外周血单核细胞相比,NLRP12在单核细胞中的表达相对较高。与 NLRP12 阴性的单核细胞相比,NLRP12 阳性的单核细胞表现出 IL18、CCL3 和 TNFA 的低表达。结构分析表明,A218V 突变以及 A218T 和 F402L 可能会降低 NLRP12 蛋白的 ATP 结合亲和力。这些发现可能会对 NLRP12-AID 的机制提供新的见解,并建议进一步研究基于 ATP 的潜在疗法。
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来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
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