Job SyndromeNCT02228941
NFIL3-induced Pathological Enhancement of IgE Class Switch Recombination in Hyper-IgE Syndrome
An observational study of Job Syndrome, run by Shanghai Children's Medical Center.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 month to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Job Syndrome
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Sep 2014to Sep 2014
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 40 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: We divided the patients with HIES into two groups, namely Autosomal-dominant Hyper-IgE Syndrome(AD-HIES) group and Autosomal-recessive Hyper-IgE Syndrome(AR-HIES) group. According to the different group, we need to do a variety of detection index, for example, gene mutations, B-lymphocyte subsets, protein expression et al.In addition, healthy control group is needed in the experiment.
Who may be able to join
- Group 1 AD-HIES patients A.Patients with extremely high serum IgE levels, IgE>2000IU/ml; B.Patients diagnosis referred to the NIH, and NIH score>15; C.Patients must be confirmed with clinical manifestations of AD-HIES, namely:skin abscesses,pneumonias,distinctive facial appearance,dental abnormalities,minimal trauma fractures D.Patients must be confirmed with STAT3 gene mutations;
- Group 2 AR-HIES patients A.Patients with extremely high serum IgE levels, IgE>2000IU/ml; B.Patients diagnosis referred to the NIH, and NIH score>15; C.Patients must be confirmed with clinical manifestations of AR-HIES, namely:pneumonias,eczema,Skin abscesses,mucocutaneous viral infections,malignancy D.Patients must be confirmed with Dedicator of cytokinesis protein 8（DOCK8） or Tyrosine Kinase 2(Tyk2) gene mutations;
- Group 3 Healthy Control A.Healthy control aged 1-25 year at time of enrollment.
Who cannot join
- Any subjects with serious conditions requiring treatment or hospitalization;
- Any subjects with pregnancy;
- Any subjects who have a history of bone marrow transplant,or have received treatment with chemotherapy or radiation;
About this study
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.
Read more
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.
- Conditions
- Job Syndrome
- Medical subject headings
- Job Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| gene mutation | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Times of Pneumonia
Measured: 1 year
Times of Skin abscess
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2014 (estimated)
- Study startSep 2014
- Primary completionSep 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Job SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- Shanghai Children's Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02228941
- Sponsor's protocol ID
- 81273314
- Status last verified
- Aug 2014
- First submitted
- 18 Aug 2014
- Last updated
- 29 Aug 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NFIL3-induced Pathological Enhancement of IgE Class Switch Recombination in Hyper-IgE Syndrome
- ClinicalTrials.gov ID
- NCT02228941
- Acronym / sponsor ID
- 81273314
- Conditions
- Job Syndrome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Shanghai Children's Medical CenterUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Sep 2014 (estimated)
- First posted
- 29 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| gene mutation | – | – |
Who may qualify
- Ages
- 1 month to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- We divided the patients with HIES into two groups, namely Autosomal-dominant Hyper-IgE Syndrome(AD-HIES) group and Autosomal-recessive Hyper-IgE Syndrome(AR-HIES) group. According to the different group, we need to do a variety of detection index, for example, gene mutations, B-lymphocyte subsets, protein expression et al.In addition, healthy control group is needed in the experiment.
Key inclusion criteria (3 listed)
- Group 1 AD-HIES patients A.Patients with extremely high serum IgE levels, IgE>2000IU/ml; B.Patients diagnosis referred to the NIH, and NIH score>15; C.Patients must be confirmed with clinical manifestations of AD-HIES, namely:skin abscesses,pneumonias,distinctive facial appearance,dental abnormalities,minimal trauma fractures D.Patients must be confirmed with STAT3 gene mutations;
- Group 2 AR-HIES patients A.Patients with extremely high serum IgE levels, IgE>2000IU/ml; B.Patients diagnosis referred to the NIH, and NIH score>15; C.Patients must be confirmed with clinical manifestations of AR-HIES, namely:pneumonias,eczema,Skin abscesses,mucocutaneous viral infections,malignancy D.Patients must be confirmed with Dedicator of cytokinesis protein 8（DOCK8） or Tyrosine Kinase 2(Tyk2) gene mutations;
- Group 3 Healthy Control A.Healthy control aged 1-25 year at time of enrollment.
Key exclusion criteria (3 listed)
- Any subjects with serious conditions requiring treatment or hospitalization;
- Any subjects with pregnancy;
- Any subjects who have a history of bone marrow transplant,or have received treatment with chemotherapy or radiation;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Times of Pneumonia
Time frame: 1 year
Times of Skin abscess
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2014.
Related trials for Job Syndrome
RecruitingPhase 1
Evaluating the Safety and Tolerability of Baricitinib in Patients With Job Syndrome With Lupus-Like Disease and/or Atopic Dermatitis
Hyper IgE Syndrome From STAT3 Mutation, Job s Syndrome
RecruitingObservational study
Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)
Infections, Pneumonia
Active, not recruitingPhase 2
Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 Deficiency
DOCK8 Deficiency
Enrolling by invitationPhase 1/2
Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
Severe Combined Immunodeficiency (SCID), Immunodeficiency With Predominant T-cell Defect, Unspecified
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Job Syndrome, run by Shanghai Children's Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Times of Pneumonia (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2014.