Leukocyte adhesion deficiency: causes, symptoms, diagnosis, treatment
Last reviewed: 23.04.2024
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Deficiency of adhesion of leukocytes (Leukocyte Adhesion Deficiency - LAD). LAD type 1 - inheritance is autosomal recessive, the disease occurs in persons of both sexes. At the heart of the disease is a mutation of the gene that codes for the beta 2 subunit of the neutrophil integrin (the central link of cellular complement-dependent interactions). The surface content of receptors participating in adhesion processes (CD11a / CD18) is sharply reduced or not determined. LAD-1 is characterized by a violation of transendothelial adhesion and chemotaxis of neutrophils, as well as the ability to digest S3-opsonized bacteria.
Deficiency of adhesion of leukocytes, caused by a defect in the structure of Sialyl-Lewis X (LAD-2). The probable type of inheritance is autosomal recessive, it is extremely rare. Defect adhesion of neutrophils LAD-2 is associated with a violation of the metabolism of fucose, probably due to a mutation of fucosyltransferase genes.
Other anomalies associated with defective mobility of neutrophils are described in a few cases.
The clinical picture of LAD depends on the severity of the defect. In patients with complete absence of CD18 / CD11b, the debut of the disease is observed in the period of the neonatal period: non-healing of the umbilical wound, omphalitis, peri-rectal cellulitis, ulcerative stomatitis, sepsis with fatal course. With a moderate defect - frequent repeated bacterial infections, mainly skin-mucous, periodontitis, sinusitis, lesions of the digestive tract (esophagitis, erosive gastritis, necrotizing enterocolitis). Characteristic of the absence of pus in the foci of inflammation. At the height of the infection, persistent leukocytosis (often hyperleukocytosis) and neutrophilia are typical, with the number of neutrophils decreasing. The clinical picture and principles of LAD-2 therapy are similar to those of LAD-1. Deficiency of fucosylation, characteristic for LAD-2, in addition to immunodeficiency manifests itself in the specific phenotype of sick children: small growth, flat face, broad bridge of nose, short extremities, wide palms, lag in mental and psychomotor development. Neutrophils of patients are not able to adhere to the vascular endothelium and penetrate the inflammatory focus.
Diagnosis of the deficit of adhesion of leukocytes type 1 is carried out on the basis of immunophenotyping of neutrophils by flow cytometry to detect a deficiency of CD 18 and CD 11b expression on their surface.
Treatment of the deficit of type 1 leukocyte adhesion is the correct tactics of antibiotic treatment during acute infections, taking into account the results of bacteriological studies and using all possibilities of arresting infections, including granulocyte transfusion. The outlook is unfavorable. Cure is possible only with the allogeneic bone marrow transplantation in the presence of a compatible donor. With moderate flow, a significant reduction in the frequency and severity of infection with adequate drug (co-trimoxazole) and dental prophylaxis is possible.
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