Leukocyte adhesion deficiency (LAD) is a defect of cellular adhesion molecules resulting in clinical syndromes. It is a combined (B cell) and cellular (T cell) immunodeficiency disorder.
Primarily, leukocytes cannot escape from the blood to tissues that have been attacked by microbes. Continuous surveillance of foreign antigens by leukocyte trafficking suffers disruption as well. There are three different types of LAD:
LAD has an autosomal recessive mode of inheritance.
Leukocyte adhesion deficiency type-1 (LAD-I) is a rare, inherited combined deficiency disorder of the immune system; it affects 1 in 1 million people annually and frequently presents with recurrent, indolent bacterial infections.
The literature review of the clinical findings of patients with LAD-I reveals that recurrent infections (93.3%) and poor wound healing (86%) are the most prevalent clinical findings. A defect in CD18 (the beta subunit of the integrins) was present in all patients.
Mortality for severe leukocyte adhesion deficiency-I was reported as 75% by the age of 2 years (in an initial 1988 multicenter retrospective evaluation). Patients with moderate disease (2% to 30% CD18-expressing neutrophils) survive childhood, with multiple infections affecting the skin and mucosal surfaces; documented mortality exceeds 50% by the age of 40 years.
Deficiency of the following integrins: LFA-1/Mac-1, p150 and p95 cause the immunologic and clinical abnormalities seen in leukocyte adhesion deficiency. These proteins functions as adhesion molecules. They are present on lymphocytes, granulocytes, monocytes, and large granular lymphocytes. LFA-1, Mac-1, and glycoprotein 150/95 have a common beta chain but have distinct alpha chains denominated M1 (Mac-1 molecule), L1 (LFA-1 molecule), and X1 (p150,95 molecules). A defect in the beta subunit is accountable for the decreased expression of LFA-1/Mac-1 polypeptide. Natural killer cell activity is not affected. The lesion is on chromosome 21, noted in some patients studied by molecular biology techniques.
Characteristically, biopsy of infected tissue demonstrates inflammatory infiltrates completely devoid of neutrophils. Remnants of the umbilical cord can show a loose edematous tissue with remarkably few inflammatory cells. In contrast, there is an elevated level of peripheral blood leucocytes (over 29000/microliters) due to an impaired mobilization of leukocytes to extravascular sites of inflammation.
The classic presentation of leukocyte adhesion deficiency is recurrent bacterial infections, neutrophil adhesion defects, and umbilical cord sloughing delays. The adhesion defects result in poor leukocyte chemotaxis, particularly the neutrophil, with an inability to form pus and neutrophilia.
Individuals with leukocyte adhesion deficiency commonly suffer from bacterial infections beginning in the neonatal period. Infections such as omphalitis, pneumonia, gingivitis, and peritonitis are common and usually life-threatening due to the inability to destroy the invading pathogens. Individuals with LAD do not form abscesses because granulocytes cannot migrate to the sites of infection.
Other miscellaneous manifestations may include:
Flow Cytometry Analysis (definitive test):
Sequence analysis using genetic testing.
Quantitative Serum Immunoglobulins.
IgG antibodies (post-immunization)
IgG antibodies (post-exposure)
Detection of isohemagglutinins (IgM)
Blood lymphocyte subpopulations
Lymphocyte stimulation assays
Nitroblue tetrazolium (NBT) test (before and after stimulation with endotoxin)
Complement System Evaluation
Measurement of individuals components by immunoprecipitation tests, ELISA, or Western blotting
Complement system functional studies
Other investigations of immunodeficiency disorders
Differentials for leukocyte adhesion deficiency include the following list of disorders:
The leukocyte adhesion deficiency prognosis varies depending on the severity of the disease; it is usually fatal before one year of age. Moderate LAD cases can live longer than the third decade of life with appropriate antimicrobial therapy. Those patients with successful allogeneic hematopoietic stem cell transplant can have a better quality of life.
The most common complications are infectious diseases affecting the skin, respiratory system, gastrointestinal system, oral cavity, and some internal organs. Leukocyte adhesion deficiency has a high mortality rate.
Consanguineous couples with an affected child should be counsel about the likelihood of having another affected child. The should counsel about patient care in health and disease.
An interprofessional team should treat a patient with leukocyte adhesion deficiency, comprised of a specialty trained genetics nurse, pediatrician, geneticist, clinical immunologist, and an infectious disease specialist. This problem is not treatable in a primary care facility. Parents of a child affected with LAD should receive counsel about the disease, and the integral management of the patient. Parents also require psychological support.
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