The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias

Ruı́z-Argüelles, Alejandro; Llórente, Luis

doi:10.1016/j.autrev.2006.09.008

Cited by 94 publications

(66 citation statements)

References 33 publications

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“…2B, inset). Meanwhile, it has been suggested that the deficient expression of mCRPs, especially CD59, is associated with autologous cell destruction by complement attack in autoimmune disorders, such as autoimmune hemolytic anemia, systemic lupus erythematosus, autoimmune thrombocytopenia, and aplastic anemia (4,5,30), possibly resulting from NF-B dysfunction due to genetic mutation (31). In addition, mouse CD59 genetic deficiency promotes atherogenesis in animal models (32); similarly, this study revealed the pathogenic roles of CD59 in atherosclerosis, a chronic inflammatory and immune vascular disease (33).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, CD59 plays a crucial role in protecting autologous cells from destruction by complement. Deficient or reduced CD59 expression in pathogens or host cells may lead to the direct lysis of invading pathogens or autologous cells in various diseases, such as autoimmune hemocytopenia and systemic lupus erythematosus (4,5). In contrast, high CD59 expression in abnormal host cells leads to the incapability of the complement system to destroy target cells and triggers comprehensive downstream pro-cell survival signaling (6).…”

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confidence: 99%

“…The activation of the complement cascade leads to the direct lysis of invading pathogens by the membrane attack complex (MAC), 4 phagocytosis opsonized by C3b/iC3b tagging, and the production of anaphylatoxins C3a/C5a; all these effects synergistically promote the clearance of foreign intruders. To prevent deleterious bystander effects on innocent host cells during this process, Ͼ10 circulating and membrane-bound complement regulatory proteins (mCRPs, including CD59) have evolved to restrict the activation of complement activation at diverse stages.…”

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confidence: 99%

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NF-κB and Enhancer-binding CREB Protein Scaffolded by CREB-binding Protein (CBP)/p300 Proteins Regulate CD59 Protein Expression to Protect Cells from Complement Attack

Teng

Wang

et al. 2014

Journal of Biological Chemistry

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Background: CD59 is the sole membrane complement regulatory protein in restricting membrane attack complex assembly. Results: CD59 gene produces eight transcripts that share three transcriptional initiation sites but the same open reading frame. Conclusion: NF-B and CREB (as an enhancer-binding protein) bridged by CBP/p300 are responsible for the inducible expression of CD59. Significance: CD59 regulation mechanism suggests potential drug targets for controlling various complement-related human diseases.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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NF-κB and Enhancer-binding CREB Protein Scaffolded by CREB-binding Protein (CBP)/p300 Proteins Regulate CD59 Protein Expression to Protect Cells from Complement Attack

Teng

Wang

et al. 2014

Journal of Biological Chemistry

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“…1 Deficient expression of the complement regulatory proteins Daf1 and CD59 have been found in human patients with autoimmune haemocytopenias, including autoimmune haemolytic anaemia, patients with autoimmune thrombocytopenia, and patients with systemic lupus erythematosus showing lymphopaenia. 2 Furthermore, it has been shown in a variety of mouse autoimmune models that Daf1 plays a protective role in autoimmune disease. [3][4][5][6][7] It has been argued that Daf1 exerts control over T-cell responsiveness in a complement-dependent manner, influencing the expression of interferon (IFN)-c and interleukin (IL)-12.…”

Section: Introductionmentioning

confidence: 99%

Decay‐accelerating factor 1 (Daf1) deficiency exacerbates xenobiotic‐induced autoimmunity

et al. 2010

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Summary Absence of decay‐accelerating factor 1 (Daf1) has been shown to enhance T‐cell responses and autoimmunity via increased expression of specific cytokines, most notably interferon (IFN)‐γ. To determine if Daf1 deficiency can exacerbate IFN‐γ‐dependent murine mercury‐induced autoimmunity (mHgIA), C57/BL6 Daf1+/+ and Daf1−/− mice were exposed to mercuric chloride (HgCl2) and examined for differences in cytokine expression, T‐cell activation and features of humoral autoimmunity. In the absence of Daf1, mHgIA was exacerbated, with increased serum immunoglobulin G (IgG), anti‐nuclear autoantibodies (ANAs) and anti‐chromatin autoantibodies. This aggravated response could not be explained by increased T‐cell activation but was associated with increased levels of IFN‐γ, interleukin (IL)‐2, IL‐4 and IL‐10 but not IL‐17 in Daf1‐deficient mice. Anti‐CD3/anti‐CD28 costimulation of Daf1−/− CD4+ T cells in vitro was also found to increase cytokine expression, but the profile was different from that of mHgIA, suggesting that the cytokine changes observed in Daf1 deficiency reflect a response to mercury. The role of Daf1 in influencing cytokine expression was further examined by stimulation of CD4+ T cells in the presence of anti‐CD3 and CD97, a molecular partner for Daf1. This resulted in increased IL‐10, decreased IL‐17 and IL‐21 and decreased IFN‐γ. These findings demonstrate that the absence of Daf1 exacerbates mHgIA, with changes in the profile of expressed cytokines. Interaction between Daf1 and its molecular partner CD97 was found to modify expression of mHgIA‐promoting cytokines, suggesting a possible approach for the suppression of overaggressive cytokine production in autoimmunity.

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“…The Pig-a gene is X-linked, and mutational inactivation of several exons in somatic cells triggers the inhibition of GPI biosynthesis, blocking the ability of CD molecules attaching to the membrane (Lucio, 2006); this inactivation leads to two relative phenotypes. A previous study has shown that CD55 and CD59 are expressed on the surface of nearly all blood cells through linkage with GPI (Ruiz-Argüelles and Llorente, 2007). The two phenotypes can be distin-guished and detected by indirect immunofluorescence staining (Kimoto et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The <i>in vivo</i> Pig-a gene mutation assay is applied to study the genotoxicity of procarbazine hydrochloride in Sprague-Dawley rats

Deng

Tan

et al. 2016

Fundam. Toxicol. Sci.

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-The Pig-a gene is well-known to encode a key enzyme essential in the biosynthesis of glycosylphosphatidylinositol (GPI), which attaches CD molecules (Cluster differentiation), such as CD55 and CD59, to red blood cells (RBCs) membranes. In this study, the blood was marked with the special antigen CD45-PE (Phycoerythrin) to separate the erythrocytes from the leukocytes, then the Pig-a mutant frequency (MF) of RBCs could be investigated without pivotal antigen CD59-FITC (Fluorescein isothiocyanate), and the optimal ENU concentration was determined to be 100 mg/kg/day. The optimal cell number to count and the stability of specimens were determined. At last, the in vivo Pig-a gene mutation assay was utilized to detect the potential genotoxicity of Cis-Dichlorodiammineplatinum (DP), Procarbazine Hydrochloride (PH), and Triptolide (TP). The results indicated that the Pig-a gene mutation obviously occurred in the PH treatment group. In the DP treatment group, an irregular shape with a slightly serrated border in erythrocytes was observed in the blood smear. However, no obvious Pig-a gene mutations were detected in the DP treatment and TP treatment groups under the experimental conditions. In conclusion, this primary in vivo Pig-a gene mutation assay will provide an easy protocol to use in screening potential genotoxic compounds.

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The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias

Cited by 94 publications

References 33 publications

NF-κB and Enhancer-binding CREB Protein Scaffolded by CREB-binding Protein (CBP)/p300 Proteins Regulate CD59 Protein Expression to Protect Cells from Complement Attack

NF-κB and Enhancer-binding CREB Protein Scaffolded by CREB-binding Protein (CBP)/p300 Proteins Regulate CD59 Protein Expression to Protect Cells from Complement Attack

Decay‐accelerating factor 1 (Daf1) deficiency exacerbates xenobiotic‐induced autoimmunity

The <i>in vivo</i> Pig-a gene mutation assay is applied to study the genotoxicity of procarbazine hydrochloride in Sprague-Dawley rats

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