Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses
Purpose. NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2024-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2024/5722548 |
| _version_ | 1797263165285728256 |
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| author | Yaoyao Shangguan Xingru Ding Le Ma Yi-Xin Cai Shulei Xiang Xiu-Feng Huang Yunyan Shen Hai-Guo Yu Wenjie Zheng |
| author_facet | Yaoyao Shangguan Xingru Ding Le Ma Yi-Xin Cai Shulei Xiang Xiu-Feng Huang Yunyan Shen Hai-Guo Yu Wenjie Zheng |
| author_sort | Yaoyao Shangguan |
| collection | DOAJ |
| description | Purpose. NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. Methods. Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. Results. Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. Conclusions. Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population. |
| first_indexed | 2024-04-25T00:08:40Z |
| format | Article |
| id | doaj.art-ff9791db539c4be88ab2417332c76bcf |
| institution | Directory Open Access Journal |
| issn | 2314-7156 |
| language | English |
| last_indexed | 2024-04-25T00:08:40Z |
| publishDate | 2024-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj.art-ff9791db539c4be88ab2417332c76bcf2024-03-14T00:00:01ZengHindawi LimitedJournal of Immunology Research2314-71562024-01-01202410.1155/2024/5722548Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation AnalysesYaoyao Shangguan0Xingru Ding1Le Ma2Yi-Xin Cai3Shulei Xiang4Xiu-Feng Huang5Yunyan Shen6Hai-Guo Yu7Wenjie Zheng8Department of Pediatric RheumatologyZhejiang Provincial Clinical Research Center for Pediatric DiseaseRheumatology and Immunology DepartmentZhejiang Provincial Clinical Research Center for Pediatric DiseaseDepartment of Nephrology and ImmunologyZhejiang Provincial Clinical Research Center for Pediatric DiseaseDepartment of Nephrology and ImmunologyRheumatology and Immunology DepartmentDepartment of Pediatric RheumatologyPurpose. NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID. Methods. Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed. Results. Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation. Conclusions. Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.http://dx.doi.org/10.1155/2024/5722548 |
| spellingShingle | Yaoyao Shangguan Xingru Ding Le Ma Yi-Xin Cai Shulei Xiang Xiu-Feng Huang Yunyan Shen Hai-Guo Yu Wenjie Zheng Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses Journal of Immunology Research |
| title | Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses |
| title_full | Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses |
| title_fullStr | Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses |
| title_full_unstemmed | Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses |
| title_short | Clinical and Genetic Spectrum of Nine Cases of NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) and Identification of One Novel NLRP3 Mutation by Genetic Variation Analyses |
| title_sort | clinical and genetic spectrum of nine cases of nlrp3 associated autoinflammatory disease nlrp3 aid and identification of one novel nlrp3 mutation by genetic variation analyses |
| url | http://dx.doi.org/10.1155/2024/5722548 |
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