| Autor: |
A K, Vaishnaw, E, Toubi, S, Ohsako, J, Drappa, S, Buys, J, Estrada, A, Sitarz, L, Zemel, J L, Chu, K B, Elkon |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
Arthritis and rheumatism. 42(9) |
| ISSN: |
0004-3591 |
| Popis: |
To determine the clinical spectrum of disease in humans with mutations in the CD95 (Fas/ APO-1) receptor and to obtain mechanistic insight into the different clinical phenotypes observed.Clinical information for each of the index cases, first-degree relatives, and any family members reported to have Canale-Smith syndrome (or another autoimmune disease) was gathered by direct interview, chart review, and verification of data by the physician or pathologist concerned. Apoptosis of activated T or B lymphocytes was induced by agonistic anti-CD95 antibodies and quantified by a cell death assay (propidium iodide staining in the subdiploid peak) or cell viability assay (alamar blue or 3H-thymidine incorporation).Evaluation of an additional 8 probands with novel heterozygous CD95 mutations revealed hypergammaglobulinemia and immune-mediated cytopenias in all patients, as well as urticarial rash, oral ulceration, lymphopenia, and peripheral neuropathy in some individuals. One patient (P4) had systemic lupus erythematosus (SLE) characterized by a World Health Organization class V lupus nephropathy, a recurrent, reversible multifocal central nervous system disorder, high-titer antiphospholipid autoantibodies, and autoimmune cytopenias. In the P4 pedigree, the father had reduced T and B cell apoptosis associated with a CD95 mutation, whereas an independent B cell apoptotic defect was demonstrated in maternal family members who did not have a CD95 mutation. Three cases of B cell lymphoma occurred in carriers of the CD95 mutation.CD95 mutations are associated with loss of regulation of B lymphocytes, which predisposes to systemic autoimmunity including SLE. The P4 family provides a model of the complex genetic and functional interactions that are required for the development of a lupus-like syndrome. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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