Leukocyte adhesion deficiency-1

A rare immunodeficiency disorder

Classification
External resources

Leukocyte adhesion deficiency-1 (LAD-1) is a rare immunodeficiency disorder characterized by the inability of leukocytes (white blood cells) to properly adhere to the endothelial cells of blood vessels. This defect impairs the normal migration of leukocytes to sites of infection, leading to recurrent bacterial infections and impaired wound healing.

Pathophysiology

LAD-1 is caused by mutations in the gene encoding the beta-2 integrin subunit, also known as CD18. This subunit is a critical component of the integrin family of adhesion molecules, which are essential for leukocyte adhesion and migration. The absence or dysfunction of CD18 results in the inability of leukocytes to adhere to the vascular endothelium, preventing their extravasation into tissues where they are needed to combat infections.

Clinical Features

Patients with LAD-1 typically present with recurrent bacterial infections, particularly of the skin and mucous membranes. Common infections include gingivitis, periodontitis, and skin abscesses. A hallmark feature of LAD-1 is the lack of pus formation at sites of infection, due to the impaired recruitment of neutrophils.

Other clinical manifestations may include delayed separation of the umbilical cord, poor wound healing, and severe periodontal disease. The severity of the condition can vary, with some patients experiencing life-threatening infections early in life.

Diagnosis

The diagnosis of LAD-1 is based on clinical presentation, laboratory findings, and genetic testing. Laboratory tests typically reveal leukocytosis (an increased number of white blood cells) and the absence of CD18 expression on leukocytes, as determined by flow cytometry. Genetic testing can confirm mutations in the CD18 gene.

Treatment

Management of LAD-1 involves aggressive treatment of infections with appropriate antibiotics and supportive care. In severe cases, hematopoietic stem cell transplantation (HSCT) may be considered as a curative treatment option. Gene therapy is an emerging area of research for the treatment of LAD-1.

Prognosis

The prognosis for individuals with LAD-1 depends on the severity of the condition and the availability of treatment. Early diagnosis and appropriate management of infections are crucial for improving outcomes. Patients with milder forms of the disease may have a better prognosis, while those with severe forms may experience life-threatening complications.

Related pages

• Immunodeficiency disorder
• Leukocyte
• Integrin
• Hematopoietic stem cell transplantation