Inherited disorder affecting leukocytes resulting in
localized bacterial infections rapidly progressing to an extensive
Lymphocyte Function-Associated Antigen-1
Immunodeficiency; LFA-1 Deficiency.
Immunologic disorder affects phagocytic properties of
leukocytes as a consequence of lack of expression of β2 integrin
CD18 (LAD I) or of its selective ligand (LAD II).
Fewer than 200 cases of LAD I and 10 cases of LAD
II have been reported in the literature. No racial predominance for LAD I;
LAD II has been reported only in people of Middle Eastern descent.
Both forms are autosomal recessive (equal
number of males and females). LAD I is caused by mutations in the gene for
CD18 (β chain of β2 integrins). Gene map locus is
21q22.3. LAD II is caused by mutations in a gene that fucosylates sialyl
Lewis X (ligand for E selectin), resulting in a defect in fucose metabolism.
β Integrins are transmembrane glycoproteins
that transmit signals from the extracellular surface to cytoskeletal
proteins, thus playing a critical role in phagocytic functions. The β2 integrin CD18 is expressed on leukocytes, and its ligands are
expressed on endothelial cells. Binding of CD18 to ligands also mediates
cytokine production, cytotoxicity, apoptosis, and proliferation. LAD I is a
result of a mutation in CD18 gene, the expression of which is severely
diminished (<1% in 75% of affected patients).
Sialylated Lewis X (SleX or CD15) is the major selectin ligand; both the
sialic acid and the fucose moieties of SleX are needed for binding to
selectins. This ligand is missing in LAD II; affected patients also have a
defect in fucose metabolism.
Neutrophilia (>20 × 109 WBC/l) in the
absence of infection; impaired microbicidal activity and oxidative responses
against bacteria and Candida (in LAD I); flow cytometry shows a considerable
decrease in β2 integrin CD18 on leukocytes (LAD I). In LAD II,
Bombay blood group phenotype is detected and biochemical activity of GMD is
Patients with LAD I present with delayed
umbilical cord separation followed by various types of localized infection
caused by Staphylococcus bacteria (plus fungal organisms, usually Candida albicans) without pus
(omphalitis, perirectal and labial cellulitis, classic infections in
neutropenic patients, otitis media with minimal inflammation, and other
indolent necrotic skin infections) prone to generalization. In less severely
affected patients, periodontitis accompanying tooth eruption and oral
ulcerations may be the presenting symptoms. Patients with severe LAD I die
before age 1 year as a consequence of severe bacterial or, less frequently,
life-threatening viral infections. Patients with LAD II do not have delayed
umbilical cord separation and usually do not die of infection. They have
severe mental retardation, neurologic impairment, and short stature.
Blood examination: white blood cells and platelet
count must be obtained. Consider fucose supplementation in patients with LAD II.
None specific. Administer broad-spectrum
IV antibiotic therapy.