Natural history and early diagnosis of LAD-1/variant syndrome
| Autor: | Aytemiz Gurgey, Charlotte M. Niemeyer, Gönül Hiçsönmez, Karl Seeger, Robin van Bruggen, Dirk Roos, Anton T.J. Tool, Nanne Kamerbeek, Taco W. Kuijpers, Arthur J. Verhoeven, A Karow, Ozden Sanal |
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| Přispěvatelé: | AII - Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology, Landsteiner Laboratory, Çocuk Sağlığı ve Hastalıkları |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Blood Platelets
Male Immunology Hemorrhage Disease Biology Biochemistry Autoantigens FERMT3 Blood cell chemistry.chemical_compound Multienzyme Complexes medicine Cell Adhesion Humans Platelet NADH NADPH Oxidoreductases Leukocyte adhesion deficiency Chemotaxis Zymosan rap1 GTP-Binding Proteins Cell Biology Hematology Bacterial Infections Syndrome Non-Fibrillar Collagens medicine.disease Pedigree Bleeding diathesis medicine.anatomical_structure rap GTP-Binding Proteins chemistry Mycoses Female Follow-Up Studies Granulocytes Signal Transduction |
| Zdroj: | Blood, 109(8), 3529-3537. American Society of Hematology |
| ISSN: | 0006-4971 |
| DOI: | 10.1182/blood-2006-05-021402 |
| Popis: | The syndrome of leukocyte adhesion deficiency (LAD) combined with a severe Glanzmann-type bleeding disorder has been recognized as a separate disease entity. The variability in clinical and cell biological terms has remained largely unclear. We present data on 9 cases from 7 unrelated families, with 3 patients being actively followed for more than 12 years. The disease entity, designated LAD-1/variant syndrome, presents early in life and consists of nonpussing infections from bacterial and fungal origin, as well as a severe bleeding tendency. This is compatible with 2 major blood cell types contributing to the clinical symptoms (ie, granulocytes and platelets). In granulocytes of the patients, we found adhesion and chemotaxis defects, as well as a defect in NADPH oxidase activity triggered by unopsonized zymosan. This last test can be used as a screening test for the syndrome. Many proteins and genes involved in adhesion and signaling, including small GTPases such as Rap1 and Rap2 as well as the major Rap activity-regulating molecules, were normally present. Moreover, Rap1 activation was intact in patients' blood cells. Defining the primary defect awaits genetic linkage analysis, which may be greatly helped by a more precise understanding and awareness of the disease combined with the early identification of affected patients. |
| Databáze: | OpenAIRE |
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