Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decay-accelerating factor (DAF, CD55) is a glycosylphosphatidylinositol-anchored membrane protein that restricts complement activation on autologous cells. It is also a ligand for CD97, an activation-associated lymphocyte antigen with seven transmembrane domains. It is widely expressed on cells of both the hematopoietic and nonhematopoietic lineages. Although deficiency of DAF on human erythrocytes is associated with the hemolytic anemia syndrome paroxysmal nocturnal hemoglobinuria, the in vivo biology of DAF is still poorly understood. We addressed the in vivo function of DAF in a knockout mouse model and describe here that deletion of DAF exacerbates autoimmune disease development in MRL/lpr mice, a model for human systemic lupus erythematosus. Compared to DAF-sufficient littermate controls, DAF-deficient female MRL/lpr mice developed exacerbated lymphadenopathy and splenomegaly, higher serum anti-chromatin autoantibody levels, and aggravated dermatitis. Consistent with the phenotype of aggravated dermatitis in DAF-deficient mice, Northern and Western blots and immunofluorescence studies showed DAF to be expressed abundantly in the mouse skin, suggesting that it may play a particularly important role in this tissue. Histology and immunostaining demonstrated inflammatory infiltrate and focal C3 deposition in early skin lesions, mostly along the dermal-epidermal junction. These results reveal a protective function of DAF in the development of a systemic autoimmune syndrome and suggest that dysfunction or down-regulation of DAF may contribute to autoimmune disease pathogenesis and manifestation.
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PMID:Deletion of decay-accelerating factor (CD55) exacerbates autoimmune disease development in MRL/lpr mice. 1221 36

CD55 and CD59 are glycosylphosphatidylinositol-anchored proteins with complement inhibitory properties. Autoimmune hemolytic anemia (AIHA) has been associated with antiphospholipid antibodies (APLA). The aim of this study was to evaluate the presence of APLA and its possible correlation with diminished CD55 and CD59 in red blood cells from patients with primary AIHA or secondary to systemic lupus erythematosus (SLE). Flow cytometric analyses were performed on CD55 and CD59 stained erythrocytes from 24 patients (primary AIHA, n=8; AIHA plus SLE, n=11; and SLE without AIHA, n=5) and 20 healthy controls. Antibodies to several phospholipids were detected in the sera by ELISA. Most patients with AIHA plus SLE and few with primary AIHA showed deficiency of either or both CD55 and CD59 expression and was not associated to the presence of APLA, while SLE patients exhibited a normal expression of these molecules. Although our findings showed CD55 and CD59 deficiency in primary or secondary AIHA, it appears that this defect plays a facilitator rather than a triggering role for the hemolytic process. Additionally, a role of anti-phospholipid antibodies as causative of this acquired defect is questionable.
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PMID:Deficiency of red cell bound CD55 and CD59 in patients with systemic lupus erythematosus. 1288 Jun 76

Although increased blood cell deficiency of glycosyl phosphatidylinositol-anchored membrane proteins has often been detected in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), the clinical significance of such paroxysmal nocturnal hemoglobinuria (PNH)-type cells remains to be elucidated. We established a sensitive flow cytometric assay capable of detecting less than 0.01% of CD59-CD55- blood cells in a sample and used the assay to examine a large number of patients with bone marrow failure. An increase in the proportion of PNH-type cells was detectable in approximately 60% of all AA patients and in 20% of all refractory anemia (RA)-MDS patients. The increase was undetectable in patients with RA with an excessive number of blasts, acute myelogenous leukemia, multiple myeloma, or systemic lupus erythematosus. Our study showed that the presence of an increased number of PNH-type cells was predictive of a good response to immunosuppressive therapy and a favorable prognosis among patients with recently diagnosed AA and RA. A sensitive flow cytometric analysis for detection of a small population of PNH-type cells in peripheral blood cells is one of the most important examinations in the management of bone marrow failure.
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PMID:Clinical significance of a small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure. 1692 32

CD55 and CD59 are glycophosphatidylinositol-anchored proteins with complement inhibitory properties. Lymphopenia in systemic lupus erythematosus (SLE) has been associated with autoantibodies targeting nuclear antigens. The aim of this study was to evaluate the surface density of CD55 and CD59 in T and B lymphocytes from patients with SLE and lymphopenia and its possible correlation with the presence of common SLE autoantibodies. Flow cytometric analyses were performed on CD55 and CD59 stained CD3+ and CD19+ cells from 40 SLE patients, 30 with lymphopenia and 10 without it, and 25 healthy controls. Autoantibodies were detected in the sera by enzyme linked immunosorbent assay. The mean fluorescence intensity of CD55 and CD59 in T and B cells was significantly diminished in SLE patients with lymphopenia when compared with healthy subjects. Interestingly, the opposite was found in T and B cells from non-lymphopenic SLE patients. Although there was no correlation between CD55 and CD59 surface density and the presence of any specificity of the autoantibodies tested, higher titres of anti-dsDNA, anti-SM and anti-ribosomal p antibodies were significantly associated with lymphopenia. The deficiency of CD55 and CD59 expression may play a role in the pathophysiology of lymphopenia, most likely by increasing the susceptibility of cells to complement mediated cytolysis.
Lupus 2006
PMID:Diminished expression of complement regulatory proteins (CD55 and CD59) in lymphocytes from systemic lupus erythematosus patients with lymphopenia. 1708 Sep 16

Mammalian cells are provided with surface-bound complement regulatory proteins that protect them from uncontrolled complement-mediated lysis. Two of these regulators in humans, CD55 and CD59, are glycosylphosphatidylinositol-anchored, type I cell surface proteins, which inhibit formation of the C3 convertases and prevent the terminal polymerization of the membrane attack complex, respectively. Paroxysmal nocturnal hemoglobinuria is a genetic disorder due to the impaired conformation of the glycosylphosphatidylinositol-anchor, that results in the deficient expression of CD55 and CD50 which leads to excessive destruction of red cells and leukocytes. We have studied the expression of these two molecules in patients with autoimmune hemolytic anemia, autoimmune thrombocytopenia, and patients with systemic lupus erythematosus showing lymphopenia, and found that all three types of cytopenias are associated to deficient expression of CD55 and CD59 on the involved hematopoietic lineage. These are the first descriptions of acquired deficiencies of complement regulatory molecules in human disease, and it seems, from our results, that such deficiencies might play a pathogenic role in the mechanism of cell destruction. Although autoantibodies appeal as the best candidates to cause underexpression of CD55 and CD59, the search for an association to the presence and titers of most frequent self-reactive antibodies has proved non-existent.
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PMID:The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias. 1728 51

The regulatory proteins CD55 and CD59 are glycolsylphosphatidylinositol-anchored, type I cell surface proteins, which inhibit formation of the C3 convertases and prevent the terminal polymerization of the membrane attack complexes, respectively. Paroxysmal nocturnal hemoglobinuria (PNH) is a genetic disorder due to the impaired conformation of the glycolsylphosphatidylinositol anchor, which results in the deficient expression of CD55 and CD59 leading to excessive destruction of red cells and leukocytes. We have studied the expression of these two molecules in red blood cells, granulocytes and platelets in patients with PNH (two patients), autoimmune hemolytic anemia (AIHA) (seven patients), autoimmune thrombocytopenia (ATP) (22 patients), systemic lupus erythematosus (SLE) (19 patients), aplastic anemia (AA) (eight patients), and Evans syndrome (ES) (two patients). A diminished expression of CD55 and CD59 was found in the three cell lines of the two patients with PNH. In the seven patients with AIHA two were found with CD59 diminished expression in red blood cells and one with CD59 diminished expression in granulocytes. In the patients with ATP one was found with CD55 diminished expression in red blood cells, one with CD59 diminished expression granulocytes and one with a CD59 diminished expression in the platelets. In the subset of patients with SLE only one was found with a CD55 diminished expression in the red blood cells. In the patients with AA, a diminished expression in red blood cells was not found; however, one patient was found with a diminished expression of CD59 in granulocytes, and one patient with a diminished expression of CD55 in the platelets. In the two patients with ES we did not found changes in the expression of CD55 and CD59. We conclude that the diminished expression of the glycolsylphosphatidylinositol-anchored type I cell surface proteins CD55 and CD59 is not specific to PNH and that it can be found in patients with a variety of autoimmune disorders. Additional studies are needed to define the role of the deficiencies of CD55 and CD59 in the pathogenesis of autoimmune hemocytopenias.
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PMID:Abnormalities in the expression of CD55 and CD59 surface molecules on peripheral blood cells are not specific to paroxysmal nocturnal hemoglobinuria. 1915 62

We report a case of a 60 year-old female with systemic lupus erythematosus (SLE) who was being managed with low-dose oral prednisolone. Four years later, she was admitted with pain in upper abdomen of 1 week duration. It was associated with ascitis and thrombocytopenia. Radiological investigations revealed portal vein thrombosis. There were no known local thrombophilic risk factors. Investigations ruled out any associated inherited or acquired hypercoagulable states. To evaluate the cause of thrombocytopenia, bone marrow aspiration was performed. Cells were subjected to flow cytometric examination, which revealed deficiency of CD55 and CD59 on granulocytes, indicating that a clone of cells with paroxysmal nocturnal haemoglobinuria had developed in this patient which had resulted in portal vein thrombosis. At this juncture, Ham test was also positive. The importance of considering rare possibilities of thrombosis at unusual site in patients with SLE is highlighted.
Lupus 2009 Jul
PMID:Development of paroxysmal nocturnal haemoglobinuria in systemic lupus erythematosus: an unusual cause of portal vein thrombosis. 1950 72

CD55 and CD59 are glycosylphosphatidylinositol-anchored proteins with complement inhibitory properties. CD55 inhibits the formation of C3 convertases, and CD59 prevents the terminal polymerisation of the membrane attack complex. It has been reported that SLE patients seems to have an acquired deficiency of these proteins associated with secondary autoimmune haemolytic anaemia and lymphopenia. The aim of this study was to evaluate the presence of altered CD55 and CD59 expression on peripheral blood cells from SLE patients. Flow cytometric analyses were performed on red and white blood cells from 23 SLE patients and 23 healthy controls. We observed more CD55- and CD59-lymphocytes (p=0.005 and p=0.019, respectively), and CD59-granulocytes (p=0.045) in SLE patients than in controls. These results suggest there is an altered pattern of CD55 and CD59 expression on the peripheral blood cells of SLE patients, and it may play a role in the cytopenias in these patients.
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PMID:Expression of CD55 and CD59 on peripheral blood cells from systemic lupus erythematosus (SLE) patients. 2072 19

CD55, CD59, CD46, and CD35 are proteins with complement regulatory (Creg) properties that ensure cell and tissue integrity when this system is activated. The aim of this study was to evaluate the Creg expression on peripheral blood cells from SLE patients and its association with cytopenia and disease activity. Flow cytometric analyses were performed on blood cells from 100 SLE patients and 61 healthy controls. Compared with healthy controls, we observed in SLE patients with lymphopenia and neutropenia decreased expression of CD55, CD59, and CD46 (P < 0.05). In SLE patients with anemia, CD59 and CD35 were decreased on red blood cells. Furthermore, there was a negative correlation between CD55 and CD59 on neutrophils and the disease activity. The results suggest there is an altered pattern of Creg expression on the peripheral blood cells of SLE patients, and the expression is correlated with disease activity and/or with activation of the complement system.
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PMID:Diminished expression of complement regulatory proteins on peripheral blood cells from systemic lupus erythematosus patients. 2276 33

CD55, CD59, CD35 and CD46 are cell membrane proteins that have regulatory properties on the activation of the complement cascade. Deficiency in the expression of these proteins may be associated with lower protection of healthy cells against complement mediated lysis and also with the accumulation of immune complexes in tissues. Few studies assess the expression of these proteins in patients with SLE and the mechanisms that regulate reduction in cellular expression, whereas its impact on manifestations of systemic lupus erythematosus is still unknown.
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PMID:The role of complement regulatory proteins in peripheral blood cells of patients with systemic lupus erythematosus: review. 2279 96


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