Leukocyte Adhesion Deficiency (LAD)
Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency disease. Our company is committed to developing cutting-edge diagnostics and therapeutics for the management of leukocyte adhesion deficiency. As your reliable partner in leukocyte adhesion deficiency research, we offer streamlined and comprehensive solutions to meet all your scientific research requirements.
Overview of Leukocyte Adhesion Deficiency
Leukocyte adhesion deficiency is a primary immunodeficiency disorder characterized by impaired immune cell function, specifically affecting leukocytes' ability to migrate and adhere to the site of infection. This condition renders individuals highly susceptible to recurrent and severe bacterial infections, particularly in soft tissues. Leukocyte adhesion deficiency is a rare disease with an estimated incidence of 1 in 100,000 people.
Fig. 1 The leukocyte adhesion cascade. (Fekadu, Julia, et al., 2022)Pathogenesis of Leukocyte Adhesion Deficiency
The two most common types of leukocyte adhesion deficiency (LAD) are LAD1 and LAD2, which are primarily caused by genetic mutations that affect the expression or function of proteins involved in leukocyte adhesion and migration.
LAD1
LAD1, the most prevalent form, is caused by mutations in the ITGB2 gene. These mutations result in the loss or dysfunction of CD18, leading to impaired expression of β2 integrins on leukocytes. Consequently, the leukocytes are unable to effectively adhere to endothelial cells and migrate to sites of infection.
LAD2
LAD2, also known as congenital disorder of glycosylation type IIc, is caused by mutations in the SLC35C1 gene. Gene mutations cause impaired glycosylation, which disrupts the expression and function of selectin ligands on leukocytes, affecting their ability to interact with endothelial cells during adhesion.
Targets of Leukocyte Adhesion Deficiency Therapy
- Integrins
Integrins are cell surface receptors that mediate the adhesion of leukocytes to endothelial cells. Targeting integrin function is expected to restore normal leukocyte adhesion in LAD. Small molecule integrin agonists are being explored as potential therapeutics for LAD1 and LAD3.
- Selectins
Selectins are adhesion molecules that facilitate leukocyte rolling and attachment to endothelial cells. Modulating selectin expression or interaction has the potential to improve leukocyte adhesion in LAD. Targeting selectin ligands and selectin-binding carbohydrates are areas of active investigation.
- Glycosylation-related Proteins
Glycosylation plays a crucial role in leukocyte adhesion and migration. Modulators targeting glycosylation defects in LAD2 aim to correct aberrant glycosylation patterns and restore normal selectin ligand expression on leukocytes, thereby improving their ability to adhere and migrate.
Our Services
Our company has established comprehensive platforms for developing rare disease diagnostics and therapies, encompassing small molecule drug, cell therapy, gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein. Through our dedicated platforms, we are fully devoted to advancing the development of innovative diagnostic tools and therapies for leukocyte adhesion deficiency.
Recognizing the significance of animal disease models in the therapy development for leukocyte adhesion deficiency, we offer our expertise in establishing animal models specifically tailored for leukocyte adhesion deficiency. These models serve as invaluable tools to facilitate the safety evaluation and pharmacokinetics study of your drug candidates.
Animal Models of Leukocyte Adhesion Deficiency
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| Our company specializes in constructing genetic engineering models of leukocyte adhesion deficiency (LAD). Our scientists introduce genetic mutations into LAD-related genes through gene targeting techniques such as homologous recombination or gene editing techniques such as CRISPR/Cas9 to replicate disease phenotypes in animals. | |||
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| Optional Species | Mice, Bovines, Canines, Zebrafish, Non-Human Primates (Monkeys), Others | ||
Regardless of your current stage of research, we offer comprehensive research services tailored to your needs. If you are interested in our services, please don't hesitate to contact us for more information and a detailed quotation regarding the specific services you require.
References
- Fekadu, Julia, et al. "Understanding the role of LFA-1 in leukocyte adhesion deficiency type I (LAD I): moving towards inflammation?" International Journal of Molecular Sciences 23.7 (2022): 3578.
- Leon-Rico, Diego, et al. "Lentiviral vector-mediated correction of a mouse model of leukocyte adhesion deficiency type I." Human gene therapy 27.9 (2016): 668-678.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.