Soluble CD59-ANTIGEN Levels Are Increased in Renal Disease Plasma (original) (raw)
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Clinical & Experimental Immunology, 2008
Protectin (CD59 antigen) is a 20-kD phosphatidyl-inositol-linked membrane protein that inhibits formation of the membrane attack complex (MAC) of complement on homologous cells. Although the antigen has been identified in a number of human tissues, until recently a functional role had been demonstrated only in circulating cells. Using immunofluorescence techniques we have shown the presence of protectin on human glomerular epithelial cells (GEC) in culture and on GEC, tubular epithelial cells and endothelial cells in frozen sections of normal human renal cortex. In addition, we present evidence that this protein functions in protection of GEC from homologous complement: cultured cells incubated with the Fab2 fragment of a monoclonal anti-protectin antibody were markedly more susceptible to killing by homologous serum than were cells in the absence of Fab2 anti-protectin. These findings suggest that this protein may be important in the maintenance of glomerular integrity in vivo, and may be of relevance in certain renal diseases.
International Journal of General Medicine
Background: Altered regulation of the complement system is associated with multiple kidney diseases. CD35, CD55 and CD59 regulate the complement system, and changes in their expression have previously been linked with kidney disease. This study assessed whether changes in the expression levels of these proteins are associated specifically with chronic kidney disease (CKD) to understand its pathogenesis. Materials and methods: Sixty CKD patients and 60 age-matched controls were enrolled and divided into two groups: Group I (n=30 pediatric patients and n=30 controls) and Group II (n=30 adult patients and n=30 controls). The expression of CD35, CD55 and CD59 on peripheral blood cells was evaluated by flow cytometry as the proportion of positive cells expressing the marker and mean fluorescence intensity (MFI), also the relation of these markers to the stage of CKD was also evaluated. Results: Pediatric and adult CKD patients had significantly lower proportion of erythrocytes expressing CD35, CD55 and CD59 than healthy controls (P<0.001). In pediatric CKD patients, there was no significant difference in the three studied markers on neutrophils, lymphocytes and monocytes. The changes in expression of CD35, CD55 and CD59 on leukocytes were more pronounced in adult patients, who had lower proportion of CD59-positive neutrophils, CD35-and CD59-positive lymphocytes, and CD59-positive monocytes, as well as lower expression of CD59 on neutrophils and monocytes than adult controls (P<0.001, P=0.019, P<0.001, P=0.026, P<0.001 and P=0.003, respectively). The eGFR directly correlated with the proportion of positivity of some of those markers on peripheral leukocytes while there was inverse correlation between the disease stage and the same markers. Conclusion: There are alterations in the patterns of expression of complement regulatory proteins CD35, CD55 and CD59 on peripheral blood cells of patients with CKD compared with healthy controls.
Primary and Secondary CD59 Deficiency
Encyclopedia of Medical Immunology
CD59 encodes a 77-amino acid glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein, synthesized as a 128-amino acid protein that includes a signal sequence and the sequence for a GPI anchor replacement. The CD59 protein, formerly known as a membrane inhibitor of reactive lysis (MIRL) and HRF20, inhibits the final and most important step of membrane attack complex (MAC) formation. Erythrocytes that are deficient in GPI-anchored membrane proteins, including CD59, undergo complement-mediated hemolysis.
The Biochemical journal, 1996
CD59 (protectin) is a glycophosphoinositol (GPI)-anchored inhibitor of the membrane attack complex of complement found on blood cells, endothelia and epithelial cells. In addition to the lipid-tailed CD59, soluble lipid-free forms of CD59 are present in human body fluids. We have investigated the detailed structural composition of the naturally occurring soluble urinary CD59 (CD59u) using peptide mapping, anion-exchange chromatography, sequential exoglycosidase digestion and matrix-assisted laser-desorption mass spectrometry (MALDI-MS). CD59u exhibited an average M(r) of 12444 in MALDI-MS. Mass analysis of the isolated C-terminal peptide (T9) indicated that a GPI-anchor (at Asn-77) without an inositol-associated phospholipid was present in soluble CD59u. By using residue-specific exoglycosidases, chemical modification and MALDI-MS structures of seven different GPI-anchor variants were determined. Variant forms of the anchor had deletions and/or extensions of one or more monosacchari...
Proceedings of the National Academy of Sciences of the United States of America, 1992
The gene for CD59 [membrane inhibitor of' reactive lysis (MIRL), protectin], a phosphatidylinositol-linked surface glycoprotein that regulates the formation of the polymeric C9 complex of complement and that is deficient on the abnormal hematopoletic cells of patients with paroxysmal nocturnal hemoglobinuria, consists of four exons saing 20 kilobases. The untransated first exon is preceded by a G+Crich promoter region that lacks a consensus TATA or CAAT motif. The second exon encodes the hydrophobic leader sequence of the protein, and the third exon encodes the aminoterminal portion of the mature protein. The fourth exon encodes the remainder of the mature protein, including the hydrophobic sequence necesry for glycosyl-phosphatidylinositol anchor attachment. The structure ofthe CD59 gene is very simlar to that encoding Ly-6, a murine glycoprotein with which CD59 has some strtural similai. The striking dmilarity in gene stre is further evidence that the two proteins belong to a superfamily of proteins that may also include the uroine activator receptor and a squid glycoprotein of unknown function.
Frontiers in immunology, 2017
Cellular protection against undesired effects of complement activation is provided by expression of membrane-bound complement regulatory proteins including CD59. This protein prevents membrane attack complex formation and is considered to be involved in graft accommodation. Also, CD59 downregulates CD4+ and CD8+ T-cell activation and proliferation. It is unknown whether CD59 expression is affected by transplantation. The aim of this study was to evaluate the quantitative CD59 antigen expression on distinct leukocyte subsets following lung transplantation ( = 26) and to investigate whether this differs from pretransplantation ( = 9). The results show that CD59 expression on leukocytes is significantly lower posttransplantation compared with healthy controls ( = 0.002) and pretransplantation ( < 0.0001). Moreover, the CD59 expression diminishes posttransplantation on all distinct lymphocyte subsets ( < 0.02). This effect appeared to be specific for CD59 since the expression of o...
Targeted deletion of the CD59 gene causes spontaneous intravascular hemolysis and hemoglobinuria
Blood, 2001
The glycolipid-anchored glycoprotein CD59 inhibits assembly of the lytic membrane attack complex of complement by incorporation into the forming complex. Absence of CD59 and other glycolipid-anchored molecules on circulating cells in the human hemolytic disorder paroxysmal nocturnal hemoglobinuria is associated with intravascular hemolysis and thrombosis. To examine the role of CD59 in protecting host tissues in health and disease, CD59-deficient (CD59−/−) mice were produced by gene targeting in embryonic stem cells. Absence of CD59 was confirmed by staining cells and tissues with specific antibody. Despite the complete absence of CD59, mice were healthy and fertile. Erythrocytes in vitro displayed increased susceptibility to complement and were positive in an acidified serum lysis test. Despite this, CD59−/− mice were not anemic but had elevated reticulocyte counts, indicating accelerated erythrocyte turnover. Fresh plasma and urine from CD59−/− mice contained increased amounts of ...
CD59 protects rat kidney from complement mediated injury in collaboration with Crry
Kidney International, 2000
CD59 protects rat kidney from complement mediated injury regulatory proteins on the plasma membrane of host in collaboration with Crry. cells. In humans, decay accelerating factor (DAF; CD55) Background. As previously reported, the membrane-bound [1], membrane cofactor protein (MCP, CD46) [2], and complement regulator at the C3 level (Crry/p65) is important CD59 [3-7] are widely distributed in many organs and in maintaining normal integrity of the kidney in rats. However, vessels and play central roles to protect host cells from the role of a complement regulator at the C8/9 level (CD59) is not clear, especially when activation of complement occurs Key words: C3, membrane attack complex, peritubular capillaries, tubulointerstitial injury, renal protective agents.