Hyper IgE Syndrome (HIES)
Hyper IgE syndrome (HIES) is an immunodeficiency disorder resulting from a genetic mutation in either STAT3 (autosomal dominant, commonly called Job's syndrome) or DOCK8. Specialized drug and therapy development services are essential to enhance and expedite HIES research. Our company is well-equipped to address your drug and therapy development requirements in HIES therapy.
Introduction to Hyper IgE Syndrome
Hyper IgE syndrome encompasses a group of rare primary immunodeficiency disorders characterized by elevated serum IgE levels, recurrent infections, and diverse clinical manifestations. The estimated incidence of HIES ranges from 1 in 100,000 to 1 in 1,000,000 individuals, with variations observed among different populations and geographic regions. Despite its rarity, HIES poses significant challenges in diagnosis and management due to its complex genetic and immunological mechanisms.
Fig. 1 Structure and mutations of STAT3. (Minegishi, Y., 2021)Pathogenesis of Hyper IgE Syndrom
- The pathogenesis of Hyper IgE Syndrome is primarily associated with mutations in the STAT3 gene, which result in defective signaling in the JAK-STAT pathway crucial for cytokine receptor functions.
- These mutations, mostly missense and in-frame deletions, produce proteins that exert a dominant negative effect, interfering with normal STAT3 activity and cytokine signaling.
- Despite these genetic disruptions, individuals with HIES maintain enough STAT3 function to support life and some developmental processes, though their immune responses are compromised.
Fig. 2 Cytokines and JAK-STAT signaling. (2. Heimall, J., et al., 2010)Diagnosis Development of Hyper IgE Syndrome
The diagnosis of Hyper IgE Syndrome has evolved significantly with advances in genetic testing. Early diagnosis often relies on the presentation, which includes recurrent skin and lung infections, and notably high levels of immunoglobulin E (IgE). Genetic testing plays a crucial role, especially in identifying mutations in the STAT3 gene, which are present in most autosomal dominant HIES cases. This molecular diagnosis confirms the syndrome and helps distinguish between different forms of the disease, such as autosomal dominant and recessive types, which are important for guiding therapy and management strategies.
Therapy Development of Hyper IgE Syndrome
Small molecules could target signaling pathways that affect immune response and inflammation. Ruxolitinib, a JAK1/2 inhibitor, has been explored for its potential to modulate the immune response in HIES. By inhibiting these kinases, Ruxolitinib can reduce the overactivation of immune cells, thereby alleviating symptoms like inflammation and recurrent infections.
For HIES, therapies could involve the use of cells that can modulate the immune system or replace dysfunctional immune components. In HIES, MSCs could potentially be used to correct immune dysregulation. These cells help in modulating inflammatory responses and enhancing the repair of tissue damage caused by chronic infections.
In HIES, monoclonal antibodies can be designed to target specific immune mediators, offering a targeted approach to modulate the immune system's behavior. Dupilumab, a monoclonal antibody against the interleukin-4 receptor alpha (IL-4Rα), can help reduce the eczematous lesions and possibly the frequency of infections in HIES iindividuals.
Gene Therapies can be caused by mutations in the STAT3 gene among others, gene therapy might involve the delivery of a correct copy of the gene to individuals' cells. Recently, the use of lentiviral vectors to introduce a functional copy of the STAT3 gene into the individual's hematopoietic stem cells. This therapy aims to restore normal function to the immune cells, addressing the root cause of the syndrome.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative HIES therapy strategies and ensure robust support throughout the process.
Platforms of Hyper IgE Syndrome Therapy Development
Animal Models of Hyper IgE Syndrome
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to HIES therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Non-Genetically Engineering Models | ||
| We provide diverse model choices customized to meet specific research needs related to HIES. These models allow researchers to simulate and study the complex biological processes associated with HIES. | ||
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| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human HIES. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- Minegishi, Y., "Hyper-IgE syndrome, 2021 update." Allergol Int, (2021). 70(4): p. 407-414.
- Heimall, J., et al., "Pathogenesis of hyper IgE syndrome." Clin Rev Allergy Immunol, (2010). 38(1): p. 32-38.
- Tsilifis, C., et al., "STAT3 Hyper-IgE Syndrome-an Update and Unanswered Questions." J Clin Immunol, (2021). 41(5): p. 864-880.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.