2/18/2014 Leukocyte Adhesion Deficiency

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Background
Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency.
[1, 2]
The clinical picture is characterized
by marked leukocytosis and localized bacterial infections that are difficult to detect until they have progressed to
an extensive level secondary to lack of leukocyte recruitment at the site of infection. Thus the infections in patients
with leukocyte adhesion deficiency act similarly as those observed in patients with neutropenia. See the images
below.
Labial ulceration f rom which Escherichia coli was cultured in an 8-month-old girl with leukocyte adhesion def iciency type 1 (LAD I). Note
the thin bluish scar at the superior aspect of the labia f rom an earlier cellulitis.
This 3-year-old girl had leukocyte adhesion def iciency type I (LAD I) with complete absence of CD18 expression. Note the typical
gingivostomatitis, which was culture-negative f or any pathogen.
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This 10-month-old patient with severe leukocyte adhesion def iciency type I (LAD I) developed a cervical adenitis caused by Klebsiella
pneumoniae. Following incision and drainage, wound healing took 4 months.
Leukocyte adhesion deficiency type I (LAD I) is a failure to express CD18, which composes the common
2
subunit of LFA1 family (2 integrins). CD11a/CD18 (LFA-1) expressed on lymphocytes is known to play an
important role in lymphocyte trafficking (adhesion to vascular endothelium), as well as interactions to antigen
presenting cells (APC). LFA-1 also plays a role of cytotoxic killing by T cells. Another member of this family is
CD11bCD18 (MacA or CR3) and CD11cCD18(CR4). These 2 members mediate leukocyte adhesions to endothelial
cells but they also serve as receptors for iC3b (inactivated C3b). These patients succumb to life-threatening
infection, usually within 2 years of life in severe cases of leukocyte adhesion deficiency I (< 1% expression of
CD18). In milder forms of leukocyte adhesion deficiency I (1-30% expression of CD8), patients may survive to
adulthood.
Leukocyte adhesion deficiency type II is extremely rare; only a handful cases have been reported and most of
them are of Middle Eastern decent. It is a defect in the expression of ligands for selectins due to lack of enzymes
required for expression of selectin ligands. Patients have leukocytosis, recurrent infections (more prominent in
infants and toddlers), and severe growth and mental retardation. This disease is a defect in fucose metabolism
(lack of fucosylation of the carbohydrate selectin ligands) that results in failure to express the ligand for E and P
selectin, sialyl Lewis-X (CD15s) expressed on leukocytes and endothelial cells. The patients are unable to
fucosylate other glycoproteins, including the H blood group polysaccharide.
Patients with leukocyte adhesion deficiency II manifest the Bombay phenotype (ie, negative for O and H blood
group antigens with potential production of anti-H antibody). The immunoglobulin M (IgM) and immunoglobulin G
(IgG) heavy chains are also not fucosylated. However, IgM and IgG serum levels are within the reference range in
patients with leukocyte adhesion deficiency II.
Leukocyte adhesion deficiency II may be classified as one of the congenital disorders of glycosylation (CDG), a
rapidly expanding group of metabolic syndromes with a wide symptomatology and severity. All stem from
dysfunctional N -glycosylation of proteins. Currently, 18 subtypes have been reported: 12 are type I (dysfunctional
lipid-linked oligosaccharide precursor synthesis), and 6 are type II (dysfunctional trimming/processing of the
protein-bound oligosaccharide), including leukocyte adhesion deficiency II (CDG-IIc).
Variants of leukocyte adhesion deficiency have also been reported, including fully expressed but nonfunctional
CD18 and an E selectin that is expressed but rapidly cleaved from the cell surface (only present in soluble form).
Another reported type of leukocyte adhesion deficiency involves dysfunction in platelet aggregation in addition to a
defect in leukocyte adhesion. Thus, patients with this type of leukocyte adhesion deficiency manifest both severe
bacterial infections and bleeding disorder. This leukocyte adhesion deficiency variant is associated with defective
expression of the Rap-1 activator CalDAG-GEFI. Rap-1 is an essential protein involved in signaling mediated by
integrins.
More than one leukocyte adhesion deficiency variant has been labeled leukocyte adhesion deficiency type III (LAD
III), creating confusion in the literature.

Author: Stephen J Nervi, MD; Chief Editor: Harumi Jyonouchi, MD more...

Updated: Apr 2, 2012
Contributor Information and Disclosures
Author
Stephen J Nervi, MD Staff Physician, Department of Dermatology, University of Medicine and Dentistry of
New Jersey-New Jersey Medical School
Stephen J Nervi, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy
of Dermatology, American Medical Association, and Sigma Xi
Disclosure: Nothing to disclose.
Coauthor(s)
Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics,
Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-
New Jersey Medical School
2/18/2014 Leukocyte Adhesion Deficiency
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Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American
Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.
Monika I Sidor, MD Resident Physician, Department of Surgery, University of Michigan at Ann Arbor Medical
School
Monika I Sidor, MD is a member of the following medical societies: Sigma Xi
Disclosure: Nothing to disclose.
Specialty Editor Board
Terry W Chin, MD, PhD Associate Director, Pediatric Allergy/Immunology/Pulmonology, Miller Children's
Hospital, Long Beach Memorial Medical Center; Associate Professor, Department of Pediatrics, University of
California, Irvine, School of Medicine
Terry W Chin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma
and Immunology, American Association of Immunologists, American College of Allergy, Asthma and
Immunology, American College of Chest Physicians, American Thoracic Society, California Thoracic Society,
Clinical Immunology Society, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
David J Valacer, MD Consulting Staff, Hoffman La Roche Pharmaceuticals
David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and
Immunology, American Academy of Pediatrics, American Association for the Advancement of Science,
American Thoracic Society, and New York Academy of Sciences
Disclosure: Nothing to disclose.
David Pallares, MD Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and
Immunology, University of Louisville School of Medicine
David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and
Immunology
Disclosure: Nothing to disclose.
Chief Editor
Harumi Jyonouchi, MD Associate Professor, Division of Pulmonary, Allergy/Immunology, and Infectious
Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-New Jersey Medical
School
Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma
and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical
Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology
and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research
Disclosure: Nothing to disclose.
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