Leukocyte adhesion deficiency

Leukocyte adhesion deficiency (LAD), is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. Leukocyte adhesion deficiency is divided into at least two subtypes: LAD1 and LAD2.

Characteristics
LAD was first recognized as a distinct clinical entity in the 1970s. The classic descriptions of LAD included recurrent bacterial infections, defects in neutrophil adhesion, and a delay in umbilical cord sloughing. The defects in adhesion result in poor neutrophil chemotaxis and phagocytosis.

Individuals with LAD suffer from bacterial infections beginning in the neonatal period. Infections such as omphalitis, pneumonia, gingivitis, abscesses, and peritonitis are common and often life-threatening due to the infant's inability to properly destroy the invading pathogens.

Cause and Genetics


Types include:

The most common type is LAD1.

The inherited molecular defect in patients with LAD is a deficiency of the β-2 integrin subunit, also called CD18, of the leukocyte cell adhesion molecule, which is found on chromosome 21. This subunit is involved in making three other proteins (LFA-1, Integrin alphaXbeta2, and Mac-1/CD3) This basically means that the gene creates a non-functioning protein. This results in the lack of important molecules which help neutrophils make their way from the blood stream into the infected areas of the body (i.e. the lungs in pneumonia). Those neutrophils which do manage to make it to the infected areas have a difficult time phagocytosing (swallowing) the bacteria. The bacteria can then proliferate, leading to symptomatic infection. The infection can spread unimpeded and cause serious injury to important tissue.

Diagnosis
Typically, diagnosis is made after several preliminary tests of immune function are made, including basic evaluation of the humoral immune system and the cell-mediated immune system. A WBC differential will reveal extremely elevated levels of neutrophils (on the order of 6-10x normal) because they are unable to leave the blood vessels. Specific diagnosis is made through monoclonal antibody testing for CR3, one of the three complete proteins which fail to form properly as a result of β-2 integrin subunit deficiency.

Treatment
Once the diagnosis of LAD is made, bone marrow transplantation is the current standard of care. However, some progress has been made in gene therapy, an active area of research.

Epidemiology
LAD is a rare disease, with an estimated prevalence of 1 in 100,000 births. There is no described racial or ethnic predilection.