Job Syndrome Clinical Trial
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 IgE levels in
STAT3-HIES patients.
In-depth insight of the pathogenic role of NFIL3 within human STAT3-HIES has great
significance in clarifying the pathogenesis of HIES and exploiting effective targeting
interventions to improve clinical outcomes. Also, it can provide valuable clues for the
clinical treatment of IgE-related diseases, such as parasite infection and malignant
diseases.
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Observational Model: Cohort, Time Perspective: Prospective
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT00006150 -
Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)
|