Abstract:
PURPOSE:This study aimed to characterize the clinical phenotype, genetic basis, and consequent immunological phenotype of a boy with severe infantile-onset colitis and eosinophilic gastrointestinal disease, and no evidence of recurrent or severe infections. METHODS:Trio whole-exome sequencing (WES) was utilized for pathogenic variant discovery. Western blot (WB) and immunohistochemical (IHC) staining were used for protein expression analyses. Immunological workup included in vitro T cell studies, flow cytometry, and CyTOF analysis. RESULTS:WES revealed a homozygous variant in the capping protein regulator and myosin 1 linker 2 (CARMIL2) gene: c.1590C>A; p.Asn530Lys which co-segregated with the disease in the nuclear family. WB and IHC analyses demonstrated reduced protein levels in patient's cells compared with controls. Moreover, comprehensive immunological workup revealed severely diminished blood-borne regulatory T cell (Treg) frequency and impaired in vitro CD4+ T cell proliferation and Treg generation. CyTOF analysis showed significant shifts in the patient's innate and adaptive immune cells compared with healthy controls and ulcerative colitis patients. CONCLUSIONS:Pathogenic variants in CARMIL2 have been implicated in an immunodeficiency syndrome characterized by recurrent infections, occasionally with concurrent chronic diarrhea. We show that CARMIL2-immunodeficiency is associated with significant alterations in the landscape of immune populations in a patient with prominent gastrointestinal disease. This case provides evidence that CARMIL2 should be a candidate gene when diagnosing children with very early onset inflammatory and eosinophilic gastrointestinal disorders, even when signs of immunodeficiency are not observed.
journal_name
J Clin Immunoljournal_title
Journal of clinical immunologyauthors
Kurolap A,Eshach Adiv O,Konnikova L,Werner L,Gonzaga-Jauregui C,Steinberg M,Mitsialis V,Mory A,Nunberg MY,Wall S,Shaoul R,Overton JD,Regeneron Genetics Center.,Shuldiner AR,Zohar Y,Paperna T,Snapper SB,Shouval DS,Baridoi
10.1007/s10875-019-00631-6subject
Has Abstractpub_date
2019-05-01 00:00:00pages
430-439issue
4eissn
0271-9142issn
1573-2592pii
10.1007/s10875-019-00631-6journal_volume
39pub_type
杂志文章abstract::The number of CD27++ plasma cells (PCs) in peripheral blood may be a valuable biomarker for systemic lupus erythematosus (SLE) disease management. More insights into the behavior of the PC population are, however, required to validate CD27 as a reliable biomarker. In the current study, we have monitored the PC compart...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
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journal_title:Journal of clinical immunology
pub_type: 临床试验,杂志文章,多中心研究
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00916700
更新日期:1990-09-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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更新日期:2013-11-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-012-9700-5
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-011-9550-6
更新日期:2011-10-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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journal_title:Journal of clinical immunology
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journal_title:Journal of clinical immunology
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journal_title:Journal of clinical immunology
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journal_title:Journal of clinical immunology
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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