1/21. 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.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
2/21. 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.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
3/21. 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.- - - - - - - - - - ranking = 123.16082513899keywords = bacterial infection, infection (Clic here for more details about this article) |
4/21. 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.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
5/21. 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.- - - - - - - - - - ranking = 2keywords = infection (Clic here for more details about this article) |
6/21. Use of differential reinforcement to treat medical non-compliance in a paediatric patient with leukocyte adhesion deficiency.Leukocyte Adhesion Deficiency (LAD) is a rare immuno-deficiency disorder which results in chronic infections, such as gingivitis, necrotic skin infections and gastrointestinal ulcers. This case describes an 18-year-old male who was non-compliant during an inpatient hospitalization with several aspects of his complex medical regimen, particularly his wound care, physical therapy and use of his crutches. The patient's dressing change protocol was task analysed in order to create a structured, predictable routine by having the subject complete small, discrete steps. A differential reinforcement programme was implemented to provide the patient with tangible reinforcement for general compliance with his treatment, including compliance with dressing changes and physical therapy. Over a 1-month period, the subject's overall compliance with his medical regimen achieved an average of approximately 87%. His compliance with physical therapy and dressing changes both improved to 87 and 80%, respectively, by the end of his hospitalization. During the last week of his hospitalization, the use of his crutches was task analysed and included in his reinforcement programme using a changing criterion design. His average use of his crutches also improved to 80%.- - - - - - - - - - ranking = 2keywords = infection (Clic here for more details about this article) |
7/21. Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene.Leukocyte adhesion deficiency type 2 (LADII) is characterized by defective selectin ligand formation, recurrent infection, and mental retardation. This rare syndrome has only been described in 2 kindreds of Middle Eastern descent who have differentially responded to exogenous fucose treatment. The molecular defect was recently ascribed to single and distinct missense mutations in a putative Golgi guanosine diphosphate (GDP)-fucose transporter. Here, we describe a patient of Brazilian origin with features of LADII. Sequencing of the GDP-fucose transporter revealed a novel single nucleotide deletion producing a shift in the open-reading frame and severe truncation of the polypeptide. Overexpression of the mutant protein in the patient's fibroblasts did not rescue fucosylation, suggesting that the deletion ablated the activity of the transporter. Administration of oral L-fucose to the patient produced molecular and clinical responses, as measured by the appearance of selectin ligands, normalization of neutrophil counts, and prevention of infectious recurrence. The lower neutrophil counts paralleled improved neutrophil interactions with activated endothelium in cremasteric venules of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, fucose supplementation induced autoimmune neutropenia and the appearance of H antigen on erythrocytes, albeit without evidence of intravascular hemolysis. The robust response to fucose despite a severely truncated transporter suggests alternative means to transport GDP-fucose into the Golgi complex.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
8/21. A novel genetic leukocyte adhesion deficiency in subsecond triggering of integrin avidity by endothelial chemokines results in impaired leukocyte arrest on vascular endothelium under shear flow.Leukocyte arrest on vascular endothelium under disruptive shear flow is a multistep process that requires in situ integrin activation on the leukocyte surface by endothelium-displayed chemoattractants, primarily chemokines. A genetic deficiency of leukocyte adhesion to endothelium associated with defective beta2 integrin expression or function (LAD-1) has been described. We now report a novel severe genetic disorder in this multistep process associated with functional defects in multiple leukocyte integrins, reflected in recurrent infections, profound leukocytosis, and a bleeding tendency. This syndrome is associated with an impaired ability of neutrophil and lymphocyte beta1 and beta2 integrins to generate high avidity to their endothelial ligands and arrest cells on vascular endothelium in response to endothelial chemoattractant signals. Patient leukocytes roll normally on endothelial selectins, express intact integrins and G protein-coupled chemokine receptors (GPCR), spread on integrin ligands, and migrate normally along a chemotactic gradient. Activation of beta2 integrins in response to GPCR signals and intrinsic soluble ligand binding properties of the very late activation antigen-4 (VLA-4) integrin are also retained in patient leukocytes. Nevertheless, all integrins fail to generate firm adhesion to immobilized ligands in response to in situ GPCR-mediated activation by chemokines or chemoattractants, a result of a primary defect in integrin rearrangement at ligand-bearing contacts. This syndrome is the first example of a human integrin-activation deficiency associated with defective GPCR stimulation of integrin avidity at subsecond contacts, a key step in leukocyte arrest on vascular endothelium under shear flow.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
9/21. chemotaxis of non-compressed blood polymorphonuclear leukocytes from an adolescent with severe leukocyte adhesion deficiency.We have defined the defect in a child with severe leukocyte adhesion deficiency-1 (LAD) as resulting from a single amino acid shift in CD18 (from a C to T mutation at position 533) that prevents heterodimerization with the CD11 antigens to produce beta(2) integrins-the first reported patient homozygous for this defect. Although beset by frequent infections, the patient has survived to adolescence despite the lack of these important adhesion molecules. Consistent with his clinical course is the ability of his PMN to respond chemotactically in slide preparations, albeit with difficulty because of their poor purchase on substrate. The operant adhesins are unknown; his polymorphonuclear leukocytes (PMN) remain chemotactically responsive in the presence of antibodies to alphavbeta(3) and beta(1) integrins and to integrin-associated protein (IAP). These findings indicate that not all patients with severe LAD are candidates for early bone marrow transplantation.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
10/21. Human memory B cells transferred by allogenic bone marrow transplantation contribute significantly to the antibody repertoire of the recipient.The bone marrow is an important source of Abs involved in long-term protection from recurrence of infections. Allogenic bone marrow transplantation (BMT) fails to restore this working memory. Attempts to overcome this immunodeficiency by immunization of the donor have not been very successful. More needs to be known about transfer of B cell memory by BMT. We tracked memory B cells from the donor to the recipient during BMT of a girl with leukocyte adhesion deficiency. vaccination of her HLA-identical sibling donor 7 days before harvest induced haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP)-specific B cells readily detectable in marrow and blood. BMT did not lead to spontaneous production of HibCP Abs, but the recipient responded well to booster immunizations 9 and 11 mo after BMT. HibCP-specific B cells were obtained 7 days after the vaccinations, and their V(H) genes were sequenced and analyzed for rearrangements and unique patterns of somatic hypermutations identifying clonally related cells. Ninety (74%) of 121 sequences were derived from only 16 precursors. Twelve clones were identified in the donor, and representatives from all of them were detected in the recipient where they constituted 61 and 68% of the responding B cells after the first and second vaccinations, respectively. No evidence for re-entry of memory clones into the process of somatic hypermutation was seen in the recipient. Thus, memory B cells were transferred from the donor, persisted for at least 9 mo in the recipient, and constituted the major part of the HibCP-specific repertoire.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
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