A New Leukocyte Hyperadhesion Syndrome of Delayed Cord Separation, Skin Infection, and Nephrosis
Leukocyte adhesion deficiency (LAD) I is a well-described genetic disorder in which leukocytes are unable to migrate to sites of inflammation due to mutations in the ITGB2 gene coding for the β subunit of β2 (CD18) leukocyte integrins. The classic symptoms of the disease present in the newborn period as failure of separation of the umbilical cord and recurrent bacterial infections, which continue throughout life. We report on a patient with these clinical manifestations but with normal ITGB2 gene sequencing excluding LAD-I, normal carbohydrate-deficient transferrin testing excluding LAD-II, and normal platelet function excluding LAD-III. With testing for CD18 integrin function by flow cytometry, adhesion assay analysis, and time-lapse microscopy, we found the patient’s T lymphocytes to express normal levels of β1 and β2 integrins but to be highly adhesive to integrin ligands and to display decreased migration compared with control T lymphocytes. The hyperadhesiveness of the cells suggests that they might be prevented from reaching infected tissues. Interestingly, administration of glucocorticoids, for the patient’s nephrotic syndrome, alleviated the patient’s chronic diarrhea and decreased the incidence of skin infections. The hyperadhesiveness rather than adhesion deficiency of the patient’s leukocytes suggests that a novel lesion in a pathway regulating integrin adhesion is responsible for the patient’s unique LAD-I–like symptoms.
- ICAM —
- intracellular adhesion molecule
- LAD —
- leukocyte adhesion deficiency
- LFA —
- lymphocyte function–associated antigen
- Accepted August 9, 2013.
- Copyright © 2014 by the American Academy of Pediatrics