1/41. Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism. Leukocyte adhesion deficiency II has been described in only 2 patients; herein we report extensive investigation of another patient. The physical stigmata were detected during prenatal ultrasonographic investigation. Sialyl-Lewis X (sLex) was absent from the surface of polymorphonuclear neutrophils, and cell binding to E- and p-selectin was severely impaired, causing an immunodeficiency. The elevation of peripheral neutrophil counts occurred within several days after birth. A severe hypofucosylation of glycoconjugates bearing fucose in different glycosidic links was present in all cell types investigated, demonstrating that leukocyte adhesion deficiency II is not only a disorder of leukocytes but a generalized inherited metabolic disease affecting the metabolism of fucose. ( info) |
2/41. Leukocyte adhesion deficiency in a child with severe oral involvement. Leukocyte adhesion deficiency is a rare inherited defect of phagocytic function resulting from a lack of leukocyte cell surface expression of beta2 integrin molecules (CD11 and CD18) that are essential for leukocyte adhesion to endothelial cells and chemotaxis. A small number of patients with leukocyte adhesion deficiency-1 have a milder defect, with residual expression of CD18. These patients tend to survive beyond infancy; they manifest progressive severe periodontitis, alveolar bone loss, periodontal pocket formation, and partial or total premature loss of the primary and permanent dentitions. We report on a 13-year-old boy with moderate leukocyte adhesion deficiency-1 and severe prepubertal periodontitis. This case illustrates the need for the dentist to work closely with the pediatrician in the prevention of premature tooth loss and control of oral infection in these patients. ( info) |
3/41. Matched unrelated donor bone marrow transplantation in leukocyte adhesion deficiency. The severe phenotype of leukocyte adhesion deficiency is a rare, congenital disorder of leukocyte function that is usually fatal in the first few years of life. Allogeneic hematopoietic stem cell transplantation currently offers the only curative approach for this disease. We describe the first successful matched unrelated donor bone marrow transplant in an infant with leukocyte adhesion deficiency. ( info) |
4/41. Leukocyte adhesion deficiency in a Norwegian boy. A Norwegian boy suffering from recurrent urinary and respiratory tract infections was examined. It was found that granulocyte random migration, respiratory burst activity and the proportions of CD11/CD18 receptor positive leukocytes were reduced, consistent with a diagnosis of leukocyte adhesion deficiency. An increased proportion of Fc gammaI-receptor-bearing granulocytes did not compensate for the CR3 deficiency. ( info) |
5/41. A novel CD18 genomic deletion in a patient with severe leucocyte adhesion deficiency: a possible CD2/lymphocyte function-associated antigen-1 functional association in humans. Leucocyte adhesion deficiency (LAD) is an autosomal-recessive genetic disease that is characterized clinically by severe bacterial infections and caused by mutations in the CD18 gene that codes for the beta2 integrin subunit. A patient with a severe LAD phenotype was studied and the molecular basis of the disease was identified as a single homozygous defect in a Herpes virus saimiri (HVS)-transformed T-cell line. The defect identified involves a deletion of 171 bp in the cDNA that encodes part of the proteic extracellular domain. This genetic abnormality was further studied at the genomic dna level and found to consist of a deletion of 169 bp (from -37 of intron 4 to 132 of exon 5), which abolishes the normal splicing and results in the total skipping of exon 5. The 171-bp shortened 'in-frame' mRNA not only resulted in the absence of CD18 expression on the cell surface but also in its absence in the cytoplasm of HVS T-cell lines. Functionally, the LAD-derived HVS T-cell lines showed a severe, selective T-cell activation impairment in the CD2 (but not in the CD3) pathway. This defect was not reversible when exogenous interleukin-2 (IL-2) was added, suggesting that there is also a functional interaction of the lymphocyte function-associated antigen-1 (LFA-1) protein in the CD2 signal transduction pathway in human T cells, as has been previously reported in mice and in the human Papillon-Lefevre syndrome. Thus, HVS transformation is not only a suitable model for T-cell immunodeficiency studies and characterization, but is also a good system for investigating the immune system in pathological conditions. It may also be used in the future in cellular models for in vitro gene-therapy trials. ( info) |
6/41. Leukocyte adhesion deficiency disorder: report of one case. In this paper, a case of leukocyte adhesion deficiency disorder confirmed by flow cytometry and leukocyte chemotaxis assays is reported. The 32-day-old female infant was admitted to our ward on account of delayed umbilical cord detachment and omphalitis. After admission, hemogram revealed severe leukocytosis (white blood cell (WBC) counts: 86,800/cumm), and there was poor clinical response to several kinds of antibiotics. The above history indicated that the patient might be a case of leukocyte adhesion deficiency disorder. A definite absence of CD11b/CD18 adhesion molecule on the patient's granulocytes and severe defects of leukocyte function demonstrated by chemotaxis, chemokinesis and zymosan-induced respiratory burst assays confirmed this diagnosis. ( info) |
7/41. Discontinuation of fucose therapy in LADII causes rapid loss of selectin ligands and rise of leukocyte counts. Leukocyte adhesion deficiency type II (LADII) is a rare inherited disorder of fucose metabolism. patients with LADII lack fucosylated glycoconjugates, including the carbohydrate ligands of the selectins, leading to an immunodeficiency caused by the lack of selectin-mediated leukocyte-endothelial interactions. A simple and effective therapy has recently been described for LADII, based on the administration of oral fucose. Parallel to this treatment the lack of E- and p-selectin ligands on neutrophils was corrected, and high peripheral neutrophil counts were reduced to normal levels. This study reports that discontinuation of this therapy leads to the complete loss of e-selectin ligands within 3 days and of p-selectin ligands within 7 days. Peripheral neutrophil counts increased parallel to the decrease of selectin ligands. Selectin ligands reappeared promptly after resumption of the fucose therapy, demonstrating a causal relationship between fucose treatment and selectin ligand expression and peripheral neutrophil counts. ( info) |
8/41. Leukocyte adhesion deficiency. Leukocyte adhesion deficiency is a rare syndrome with autosomal recessive pattern of inheritance. An eleven-month-old boy, whose parents were first degree relatives, was referred to clinic with recurrent episodes of pneumonia, otitis and extensive necrotic wounds of perianal area since neonatal period. His umbilical cord had separated 30 days after birth. Laboratory findings included marked leukocytosis, chemotaxis abnormality, and very low levels of CD 11 (0.5%) and CD 18 (2%). Leukocyte Adhesion Defect (LAD) is rare genetic defect of a group of leukocyte membrane glycoproteins. LAD affects nearly one out of every million individuals and is characterized by recurrent bacterial and fungal infections of skin and mucous membranes, diminished pus formation, delayed umbilical cord separation, granulocytosis, poor wound healing and progressive periodontitis. This is the first report of a case of LAD in Isfahan of iran. ( info) |
9/41. Nonopsonic phagocytosis of Pseudomonas aeruginoas: insights from an infant with leukocyte adhesion deficiency. Children with leukocyte adhesion deficiency type I are at risk for overwhelming infection because their neutrophils lack surface beta 2 integrins (CD18/CD11) that normally interact with endothelial cell adhesion molecules and mediate migration to sites of bacterial invasion. in vitro studies of phagocytic cells from an infant with leukocyte adhesion deficiency type I demonstrated that complement receptor 3 (CD18/CD11b) mediates nonopsonic phagocytosis of some pseudomonas aeruginosa strains and might play a control role in the control of pseudomonas infections at sites where there are low levels of opsonins. ( info) |
| Leukocyte adhesion deficiency 1 (LAD-1) is characterized by absent or dysfunctional beta2 integrin (CD18), leading to defective chemotaxis, adherence, phagocytosis, and bacterial killing. colitis, except for rare intestinal necrotizing events, is not a well-recognized feature of this immunodeficiency. A case of nonspecific colitis clinically resembling Crohn's disease in a patient with the severe form of LAD-1 (0.5% < CD18) has been previously reported. We describe an adult patient with the moderate form of LAD-1 and chronic colitis characterized by extensive inflammation and ulceration of the right colon and terminal ileum, leading to adhesions and strictures. The chronic colitis described in this article associated with the dysfunctional neutrophils of LAD-1 represents a distinct pathology from the commonly encountered forms of inflammatory bowel disease (IBD). The existence of active IBD in the presence of dysfunctional CD18/CD11(a-b) intercellular adhesion molecules (ICAM-1) interaction is relevant to the proposed targeting of ICAM-1 for the treatment of Crohn's disease. ( info) |