title: A new leukocyte hyperadhesion syndrome of delayed cord separation, skin infection, and nephrosis.
abstract: 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.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216. oabdulrahman@prevmed.umsmed.edu.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Simpson
authors.forename: Nancy
authors.initials: N
authors.lastname: Hogg
authors.forename: Lena M
authors.initials: LM
authors.lastname: Svensson
authors.forename: Alison
authors.initials: A
authors.lastname: McDowall
authors.forename: William
authors.initials: W
authors.lastname: Daley
authors.forename: Kilby
authors.initials: K
authors.lastname: Yarbrough
authors.forename: Omar A
authors.initials: OA
authors.lastname: Abdul-Rahman
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D018821:CD18 Antigens / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005819:Genetic Markers; D006801:Humans; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D009404:Nephrotic Syndrome / Q000209:etiology; D017192:Skin Diseases, Bacterial / Q000209:etiology; D013601:T-Lymphocytes / Q000502:physiology*; D014470:Umbilical Cord / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D018821:CD18 Antigens; D005819:Genetic Markers
keywords: genetics; glucocorticoids; leukocytes; nephrotic syndrome