CD18 is a protein found on the surface of various immune cells, particularly white blood cells (leukocytes). This protein plays an important role in the body’s defense system, enabling these cells to interact with their surroundings and coordinate effective immune responses. Without proper CD18 function, the immune system’s ability to combat infections is impaired, underscoring its importance.
The Nature of CD18
CD18 is known as integrin beta chain-2 (β2) and is encoded by the ITGB2 gene in humans. It does not function alone but serves as a common subunit that combines with different alpha (α) subunits to form a family of cell adhesion molecules called β2 integrins. These include complexes such as Lymphocyte Function-Associated Antigen-1 (LFA-1, formed with CD11a), Macrophage-1 antigen (Mac-1, formed with CD11b), and p150,95 (formed with CD11c).
These integrins are transmembrane proteins that span the cell membrane, facilitating communication between the cell’s interior and its external environment. The formation of these heterodimers—each consisting of one CD18 beta subunit and one of the four CD11 alpha subunits (CD11a, CD11b, CD11c, or CD11d)—is important for their function. Their presence is widespread across various white blood cells, including neutrophils, monocytes, macrophages, and lymphocytes.
CD18’s Role in Immunity
CD18-containing integrins play a key role in the immune system, primarily by mediating cell adhesion. This adhesion allows immune cells to stick to other cells and to the extracellular matrix. This ability to adhere is important for immune cell migration, which is how these cells move from the bloodstream to sites of infection or inflammation.
An example of this migration is diapedesis, where white blood cells exit blood vessels to reach infected tissues. During this process, CD18 integrins on the surface of neutrophils bind to adhesion molecules like ICAM-1 (Intercellular Adhesion Molecule-1) on the endothelial cells lining blood vessels. This attachment allows neutrophils to resist blood flow and move through the vessel wall into the affected area.
Beyond migration, these integrins facilitate communication between immune cells, which supports a coordinated immune response. For example, LFA-1 (CD11a/CD18) on T cells and B cells binds to ICAM-1 on antigen-presenting cells, forming an “immune synapse” that enables lymphocyte activation and proliferation. Mac-1 (CD11b/CD18) on macrophages and neutrophils recognizes various ligands, including complement fragments and fibrinogen, aiding in the phagocytosis (engulfment) of pathogens and cellular debris.
Leukocyte Adhesion Deficiency Type I (LAD-I): A Consequence of Faulty CD18
When CD18 is deficient or non-functional, the immune system’s ability to respond to threats is impaired, leading to a rare genetic disorder called Leukocyte Adhesion Deficiency Type I (LAD-I). This condition is caused by mutations in the ITGB2 gene, which codes for the CD18 protein. The lack of functional CD18 means that white blood cells cannot properly adhere to blood vessel walls or migrate into tissues, making the body susceptible to infections.
Individuals with LAD-I often present with recurrent and severe bacterial and fungal infections, particularly affecting the skin, mouth, and respiratory tract. A hallmark symptom is delayed umbilical cord separation, occurring more than three weeks after birth (compared to the usual one to two weeks). Infected areas may lack typical signs of inflammation (swelling, redness, heat, pus) because immune cells cannot reach the site. Poor wound healing and severe periodontitis, leading to early tooth loss, are also common.
Diagnosis of LAD-I often involves blood tests that show a persistently high white blood cell count (leukocytosis), even without active infection. Flow cytometry is used to measure the expression of CD18 on the surface of leukocytes, revealing reduced or absent protein. Genetic testing of the ITGB2 gene can confirm the diagnosis. While prophylactic antibiotics manage infections, the only definitive treatment for LAD-I is hematopoietic stem cell transplantation, which replaces faulty immune cells with healthy ones. Gene therapy is also an area of ongoing research.