Saint-Petersburg State Pediatric Medical University, Litovskaya 2, Saint-Petersburg, 194100, Russian Federation.
N.N. Petrov Institute of Oncology, Saint-Petersburg, Russian Federation.
Rheumatol Int. 2018 May;38(5):887-893. doi: 10.1007/s00296-018-4002-8. Epub 2018 Mar 2.
NLRP12-related autoinflammatory disease (NLRP12-AID) is an exceptionally rare autosomal dominant disorder caused by germline mutations in NLRP12 gene. Very few patients with NLRP12-AD have been identified worldwide; therefore, there is a scarcity of data on phenotypic presentation of this syndrome. Here we provide evidence that NLRP12-AID may have clinical manifestations characteristic for primary immune deficiencies (PID). 246 children with periodic fever (PF) of unknown origin were subjects to the next generation sequencing (NGS) analysis; 213 of these patients had signs of primary immunodeficiency (PID) manifested by recurrent infections, while 33 kids had isolated PF. The NGS panel was composed of 302 genes implicated in PID and/or AID. 15 patients (9 girls and 6 boys) with NLRP12-AID were identified. Median age of first AID-related fever episode was 12 months, ranging from 2 months to 13 years. Main clinical features of NLRP12-related AID were periodic fever (100%), abdominal pain and diarrhea (47%), arthralgia (20%), headache (20%) and failure to thrive (33%). Nine patients demonstrated increased susceptibility to infection and two children suffered from Crohn's disease. Administration of short courses of NSAID or corticosteroids resulted in resolution of the disease flare. In one severe case, canakinumab (anti-interleukin-1β antibody) was successfully used. Significant number of patients with genetically assigned diagnosis of NLPR12-AID has clinical features which close resemble primary immune deficiency. This phenotypic overlap may result in underdiagnosis of NLPR12-AID among patients with PID.
NLRP12 相关自身炎症性疾病（NLRP12-AID）是一种由 NLRP12 基因突变引起的罕见常染色体显性遗传病。全球仅有极少数 NLRP12-AD 患者被确认；因此，对于这种综合征的表型表现，数据非常有限。在这里，我们提供证据表明 NLRP12-AID 可能具有原发性免疫缺陷（PID）的临床表现特征。我们对 246 名不明原因周期性发热（PF）的儿童进行了下一代测序（NGS）分析；其中 213 名患者有反复感染的迹象，表现为原发性免疫缺陷（PID），而 33 名儿童仅有孤立性 PF。NGS 面板由 302 个与 PID 和/或 AID 相关的基因组成。我们鉴定出了 15 名 NLRP12-AID 患者（9 名女孩和 6 名男孩）。首次发生 AID 相关发热的中位年龄为 12 个月，范围从 2 个月到 13 岁。NLRP12 相关 AID 的主要临床特征为周期性发热（100%）、腹痛和腹泻（47%）、关节炎（20%）、头痛（20%）和生长发育迟缓（33%）。9 名患者表现出对感染的易感性增加，2 名儿童患有克罗恩病。短期使用非甾体抗炎药或皮质类固醇可缓解疾病发作。在一例严重病例中，成功使用了卡那单抗（抗白细胞介素-1β抗体）。具有基因诊断 NLRP12-AID 的患者中有相当数量的人具有与原发性免疫缺陷相似的临床特征。这种表型重叠可能导致在 PID 患者中 NLRP12-AID 的诊断不足。
