Leukocyte Adhesion Deficiency (LAD)
Leukocyte adhesion deficiency (LAD) is classified as one of the primary immunodeficiency diseases. We are focused on creating innovative diagnostics and therapeutics to help manage leukocyte adhesion deficiency. As a trusted partner in your leukocyte adhesion deficiency research, we provide efficient, complete solutions tailored to all of your scientific research needs.
Overview of Leukocyte Adhesion Deficiency
Leukocyte adhesion deficiency, an immunologic disorder, is primarily due to the defect in the functions of the immune cells and more specifically due to the impairment in the migration and adherence of the leukocytes. This condition makes individuals vulnerable to frequent and serious bacterial infections, especially soft tissue infections. This form of illness is classified as a rare disease, with its prevalence being one in every one hundred thousand individuals.
Fig. 1 The leukocyte adhesion cascade. (Fekadu, Julia, et al., 2022)Pathogenesis of Leukocyte Adhesion Deficiency
The most common forms of leukocyte adhesion deficiency (LAD) are LAD1 and LAD2. Both are primarily due to genetic mutations that alter the expression or the activity of proteins responsible for the adhesion and migration of the leukocytes.
LAD1
LAD1 is the most common type, and its etiology involves mutations of the ITGB2 gene. This mutation leads to the loss or functional impairment of CD18, which in turn hinders β2 integrin expression on leukocytes. As a result, the leukocytes cannot adhere to the endothelial cells and migrate to infection sites as they should.
LAD2
Also known as a congenital disorder of glycosylation type II c, LAD2 occurs due to mutations of the SLC35C1 gene. Such mutation leads to defective glycosylation whereby a specific subset of selectin ligands on leukocytes are neither expressed nor functional, and as such, the endothelial leukocyte adhesion is compromised.
Targets of Leukocyte Adhesion Deficiency Therapy
- Integrins
Integrins are receptors on the cell surface that mediate adhesion of leukoctyes to endothelial cells. This actively participates in inflammation and leukocyte adhesion. Integrin function modulation is expected to alleviate the impairment of leukocyte adhesion in LAD. Small molecule Integrin agonists are being developed to treat LAD1 and LAD3.
- Selectins
Selectins are adhesion molecules responsible for the rolling of leukocytes and their attachment to the endothelium. Altering the expression or binding activity of selectins may increase adhesion of leukocytes in LAD complicated by hyporesponsiveness. Modification of selectin ligands and carbohydrates that bind to selectins is one of the urgent problems of scientific research.
- Glycosylation-related Proteins
Glycosylation, as it relates to immune response, involves the modification of proteins to facilitate adhesion and motility of the leukocytes. Both probes of LAD2 that rectify glycosylation errors seek to remediate the aberrant glycosylation in LAD2, which makes it possible to achieve normal expression of selectin ligands on leukocytes to increase their adhesion and migration properties.
Our Services
Our company has put together integrated platforms for developing rare disease diagnostics and therapies that include small molecule drug, cell therapy, gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein. Through our platforms, we are focused on developing advanced diagnostic and treatment methods for leukocyte adhesion deficiency.
Understanding the central role that animal disease models play in therapy development for leukocyte adhesion deficiency, we offer our services in development of animal models of leukocyte adhesion deficiency. These models are invaluable for the safety evaluation and pharmacokinetics study of your drug candidates.
Animal Models of Leukocyte Adhesion Deficiency
| Genetically Engineered Models | |||
|---|---|---|---|
| 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 to replicate disease phenotypes in animals. | |||
| Optional Models |
|
|
|
| Optional Species | Mice, Bovines, Canines, Zebrafish, Non-Human Primates (Monkeys), Others | ||
We provide diagnostic and research services starting from basic and intermediate stages of research encompassing the completion of set goals and objectives. 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.