Leukozytenadhäsionserkrankungen

Leukozytenadhäsionsdefekte, often abbreviated as LADs, are a group of rare, inherited primary immunodeficiencies. These disorders affect the function of leukocytes, specifically their ability to adhere to and migrate out of blood vessels into tissues. This crucial process, known as extravasation, is essential for mounting an effective immune response against invading pathogens.

The underlying cause of LADs is a defect in the expression or function of adhesion molecules, primarily integrins, on the surface of white blood cells. These molecules are vital for leukocytes to bind to the endothelial cells lining blood vessels. Without proper adhesion, leukocytes cannot reach sites of infection or inflammation, leading to recurrent and severe bacterial and fungal infections.

There are primarily two types of LADs. LAD-I is caused by mutations in the gene encoding the beta-2 subunit of integrins, affecting molecules like LFA-1 and Mac-1. LAD-II is characterized by a defect in fucose metabolism, impairing the synthesis of sialyl-Lewis X, a ligand for selectin molecules. A rarer form, LAD-III, involves defects in integrin activation.

Clinical manifestations of LADs include recurrent infections, particularly of the skin, respiratory tract, and gastrointestinal tract. Patients often experience impaired wound healing, gingivitis, and delayed separation of the umbilical cord. The severity of symptoms can vary depending on the specific type and genetic mutation. Diagnosis involves clinical evaluation, blood tests to assess leukocyte counts and the presence of specific adhesion molecules, and genetic testing. Treatment focuses on preventing and managing infections with antibiotics and, in severe cases, hematopoietic stem cell transplantation may be considered as a curative option.