1/6. Dysfunctional LAD-1 neutrophils and colitis.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.- - - - - - - - - - ranking = 1keywords = inflammation (Clic here for more details about this article) |
2/6. aggressive periodontitis of the primary dentition associated with idiopathic immune deficiency: case report and treatment considerations.The present case, of a child with an idiopathic immune deficiency and aggressive periodontitis in the primary dentition, serves as an example for the treatment considerations in these cases. Extraction of all the primary teeth proved to be the most adequate treatment. It allowed the child to eat properly and prevented unwanted infections that could endanger the life of the child. The newly erupted permanent teeth have been subjected to careful oral hygiene, clorhexidine topical applications, and have mild gingival inflammation and no attachment loss.- - - - - - - - - - ranking = 1keywords = inflammation (Clic here for more details about this article) |
3/6. A 19-year-old man with leucocyte adhesion deficiency. in vitro and in vivo studies of leucocyte function.We describe a male patient with leucocyte adhesion molecule deficiency (LAD) of moderate phenotype. Although diagnosis was made only 2 years before his death, the patient survived until 19 years of age. This enabled us to perform a number of novel investigation, both in vivo and in vitro, relating to his leucocyte biology. monocytes cultured in vitro matured into morphologically normal, phagocytically capable macrophages, which were able to recognize aged 'apoptotic' neutrophils. By injection of radiolabelled autologous neutrophils we demonstrated a prolonged neutrophil half-life, but normal margination, de-margination on exercise, and splenic pooling. Neutrophil adherence in vitro to vascular endothelium was normal. Histological examination of the patient's lungs at post-mortem showed intravascular aggregation of polymorphonuclear leucocytes but a paucity of cells in the interstitium and alveolar spaces. These findings indicate that the peripheral blood leucocytosis commonly observed in these patients may be due to prolonged intravascular neutrophil survival, and suggest that CD11/18 molecules have an important role in facilitating neutrophil emigration from blood vessels at sites of inflammation.- - - - - - - - - - ranking = 1keywords = inflammation (Clic here for more details about this article) |
4/6. Leukocyte adhesion deficiency (LAD) II.The occurrence of recurrent bacterial infections, neutrophil motility dysfunction and normal expression of beta 2 integrins (CD18) in two unrelated children suggested an as yet undescribed adhesion deficiency. The fact that both children exhibited the rare Bombay blood group and were Lewis negative, each involving carbohydrates with different fucose linkages, suggested a possible defect in the fucose-containing ligand for E- and p-selectin, sialyl Lewis X (SLe(x)). Using a monoclonal anti-SLe(x) antibody, we did not detect expression of SLe(x) on the neutrophils of the patients. Adhesion of neutrophils to endothelial cells activated with interleukin-1 beta or histamine was markedly decreased ( < 5% of control). The observation that the neutrophils did not bind to recombinant e-selectin and purified p-selectin confirmed the SLe(x) deficiency as the basis for adhesion deficiency. Using several in vivo techniques, we were able to show that neutrophil rolling, the first step in their adhesion, is markedly decreased, and therefore neutrophil emigration through the endothelium and arrival at site of inflammation is significantly diminished (1-2% of normal). Low binding of fucose-specific lectins to the patients' B lymphocytes transformed with Epstein-Barr virus was observed, while the binding of mannose-specific lectins was normal, providing further evidence for a general fucose deficiency as the primary defect. The existence of the patients and their deficiency emphasizes the essential role of the endothelial cell selectins and their ligand, SLe(x), in recruitment of neutrophils to sites of infection.- - - - - - - - - - ranking = 1keywords = inflammation (Clic here for more details about this article) |
5/6. Leukocyte adhesion deficiency type 1 (LAD-1)/variant. A novel immunodeficiency syndrome characterized by dysfunctional beta2 integrins.Leukocyte adhesion deficiency (LAD) is characterized by the inability of leukocytes, in particular neutrophilic granulocytes, to emigrate from the bloodstream towards sites of inflammation. Infectious foci are nonpurulent and may eventually become necrotic because of abnormal wound healing. LAD-1 is characterized by the absence of the beta2 integrins (CD11/CD18) on leukocytes. When expression is completely absent, patients often die within the first year. However, low levels of beta2 expression may result in a milder clinical picture of recurrent infection, which offers a better prognosis. In this paper, we describe the in vivo and in vitro findings on a patient with clinical features of a mild LAD-1 disorder, i.e., suffering from bacterial infections without apparent pus formation in the presence of a striking granulocytosis, showing no delayed-type hypersensitivity reaction upon skin testing, no specific antibody generation, but normal in vitro T cell proliferation responses after immunization. Expression levels of CD11/CD18 proteins were completely normal, but leukocyte activation did not result in CD11/ CD18 activation and high-avidity ligand-binding. in vitro chemotaxis and endothelial transmigration of the neutrophils as well as leukocyte aggregation responses were almost absent. On the other hand, beta1 and beta3 integrin-mediated adhesion functions were completely normal. During follow-up, a bleeding tendency related to decreased beta3 activation became clinically apparent, different from previously described cellular adhesion molecule variants. Therefore, this is the first well-documented case of a clinical combined immunodeficiency syndrome that results from nonfunctional CD11/CD18 molecules, and thus designated LAD-1/ variant.- - - - - - - - - - ranking = 1keywords = inflammation (Clic here for more details about this article) |
6/6. pyoderma gangrenosum in a child with congenital partial deficiency of leucocyte adherence glycoproteins.Congenital deficiency of beta 2 integrin leucocyte adhesion molecules is a rare immunodeficiency and is often fatal. neutrophils are unable to bind to ligands on the endothelium, and so cannot leave the circulation during inflammation or infection. When leucocyte adhesion deficiency (LAD) is caused by abnormally low expression of beta 2 integrins, it is termed LAD type 1. We describe a 5-year-old girl with a history of recurrent bacterial infections since early childhood who developed necrotic skin ulcers resembling pyoderma gangrenosum and a persistent circulating neutrophilia. Histologically, the lesions showed deep ulceration with a diffuse lymphohistiocytic infiltrate, but with a relative sparsity of neutrophils. Subsequent investigation revealed a complete absence of CD11a/CD18 beta 2 integrins on the surface of the patient's neutrophils, confirming the diagnosis of LAD type 1. The ulcers responded to treatment with oral prednisolone and colchicine.- - - - - - - - - - ranking = 1keywords = inflammation (Clic here for more details about this article) |