Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational [Patient Registry]
Official Title:
Brief Summary:
Hyper IgE syndrome (HIES) is a rare and complex primary immunodeficiency that affects multiple systems. It is characterized by elevated Immunoglobulin E(IgE), recurrent skin and pulmonary infections and eczematoid dermatitis.Somatic manifestations include scoliosis, joint hyperextensibility, impaired shedding of deciduous teeth and facial dysmorphism.
The reason of extremely high level of serum IgE in the patients with HIES is unknown. Signal transducers and activators of transcription 3(STAT3) gene mutations can cause the STAT3/Janus kinase(STAT3/JAK) signal transduction pathway disorder, then can affect the B cell development.
It is reported that levels of extracellular signal cytokine and the prolonged half-life of IgE are not the causes of dramatically increased IgE levels in STAT3-HIES patients. According to our preliminary work, we found that the slight increase of IgE-secreting plasma cells could not explain the tremendously increased IgE level and that the key class switch recombination enzyme (AID) was up-regulated in STAT3-HIES patients. Intriguingly, we found that deregulation of immunoglobulin class switch recombination (CSR) in IgE secreting plasma cells in STAT3-HIES patients might play a key role in dramatically increased IgE levels.
Nuclear factor IL-3 regulated (NFIL3) is a newly discovered transcriptional factor. During STAT3-HIES IgE-secreting plasma cells differentiating, NFIL3 was significantly upregulated. The CSR of IgE was down-regulated in STAT3-deficiency mice as well as NFIL3-deficiency mice, however Interleukin-4（IL-4）, a STAT3-independent cytokine, promotes NFIL3 expression by Signal transducers and activators of transcription 6(STAT6) dependent manner. Thus, we hypothesize that NFIL3 may play a key role in dramatically increased I