期刊
CLINICAL IMMUNOLOGY
卷 200, 期 -, 页码 55-63出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2019.01.002
关键词
Ataxia-telangiectasia; Hyper-IgM; CD38(lo)CD21(-/low) B cells; T-bet; Fas; Tregs; Tfh; gamma delta T cells
类别
资金
- Grifols
- Joanne Siegel Fund
- Dreizessen Fund
- NIAMS [T32 AR007107-41]
- NIAID [R01 AI071087]
- NIH [HL -36577, AI -77609]
Ataxia-Telangiectasia (AT) is an immunodeficiency most often associated with T cell abnormalities. We describe a patient with a hyper-IgM phenotype and immune cell abnormalities that suggest a distinct clinical phenotype. Significant B cell abnormalities with increased unswitched memory B cells, decreased naive transitional B cells, and an elevated frequency of CD19(+)CD381(lo)CD27(-)CD10(-)CD21(-/low) W B cells expressing high levels of T-bet and Fas were demonstrated. The B cells were hyporesponsive to in vitro stimulation through the B cell receptor, Toll like receptors (TLR) 7 and 9, and CD40. T cell homeostasis was also disturbed with a significant increase in gamma delta T cells, circulating T follicular helper cells (Tfh), and decreased numbers of T regulatory cells. The ATM mutations in this patient are posited to have resulted in the perturbations in the frequencies and distributions of B and T cell subsets, resulting in the phenotype in this patient. Key messages: A novel mutation creating a premature stop codon and a nonsense mutation in the ATM gene are postulated to have resulted in the unique clinical picture characterized by abnormal B and T cell populations, lymphocyte subset dysfunction, granuloma formation, and a hyper-IgM phenotype. Capsule summary: A patient presented with ataxia-telangiectasia, cutaneous granulomas, and a hyper-IgM phenotype; a novel combination of mutations in the ATM gene was associated with abnormal distributions, frequencies, and function of T and B lymphocyte subsets.
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