File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The genetic and clinical characteristics and effects of Canakinumab on cryopyrin-associated periodic syndrome: a large pediatric cohort study from China

TitleThe genetic and clinical characteristics and effects of Canakinumab on cryopyrin-associated periodic syndrome: a large pediatric cohort study from China
Authors
KeywordsCanakinumab
cryopyrin-associated periodic syndrome
genotype and phenotype correlation
novel mutation
somatic mosaicism mutation
Issue Date21-Sep-2023
PublisherFrontiers Media
Citation
Frontiers in Immunology, 2023, v. 14 How to Cite?
Abstract

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.


Persistent Identifierhttp://hdl.handle.net/10722/339200
ISSN
2023 Impact Factor: 5.7
2023 SCImago Journal Rankings: 1.868
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShu, Zhou-
dc.contributor.authorZhang, Yue-
dc.contributor.authorHan, Tongxin-
dc.contributor.authorLi, Yan-
dc.contributor.authorPiao, Yurong-
dc.contributor.authorSun, Fei-
dc.contributor.authorMa, Jin-
dc.contributor.authorMo, Wenxiu-
dc.contributor.authorSun, Jiapeng-
dc.contributor.authorChan, Koon-Wing-
dc.contributor.authorYang, Wanling-
dc.contributor.authorLau, Yu-Lung-
dc.contributor.authorMao, Huawei -
dc.date.accessioned2024-03-11T10:34:39Z-
dc.date.available2024-03-11T10:34:39Z-
dc.date.issued2023-09-21-
dc.identifier.citationFrontiers in Immunology, 2023, v. 14-
dc.identifier.issn1664-3224-
dc.identifier.urihttp://hdl.handle.net/10722/339200-
dc.description.abstract<p>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 <em>NLRP3</em> 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 <em>NLRP3</em>, 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.</p>-
dc.languageeng-
dc.publisherFrontiers Media-
dc.relation.ispartofFrontiers in Immunology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCanakinumab-
dc.subjectcryopyrin-associated periodic syndrome-
dc.subjectgenotype and phenotype correlation-
dc.subjectnovel mutation-
dc.subjectsomatic mosaicism mutation-
dc.titleThe genetic and clinical characteristics and effects of Canakinumab on cryopyrin-associated periodic syndrome: a large pediatric cohort study from China-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fimmu.2023.1267933-
dc.identifier.scopuseid_2-s2.0-85173289534-
dc.identifier.volume14-
dc.identifier.eissn1664-3224-
dc.identifier.isiWOS:001075470400001-
dc.identifier.issnl1664-3224-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats