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Entity | Paroxysmal nocturnal hemoglobinuria (PNH) |
Note | Decrease or absence of glycosylphosphatidylinositol-anchored molecules from the surface of the affected cells, such as CD59 (and CD55), resulting in chronic intravascular hemolysis, cytopenia and increased tendency to thrombosis, venous thrombosis, deficient hematopoiesis and, rarely, leukemic conversion. |
Disease | PNH involves the defective synthesis of a glycosylphosphatidylinositol (GPI) anchor that is used by certain surface proteins for tethering to the cell membrane, such as CD59 (Meri and Jarva, 1998). Somatic mutations in the X-linked gene PIGA (GPI complementation group A) which encodes a protein required in the biosynthesis of GPI molecules, have been strongly implicated in the pathogenesis of PNH (Rosti, 2000). |
Prognosis | Poor. |
Oncogenesis | Possible association between paroxysmal nocturnal hemoglobinuria phenotype and lymphoproliferative syndromes (Meletis et al., 2001). |
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Entity | Alzheimer's disease (AD) |
Note | It was demonstrated at both protein and mRNA levels that CD59 expression in frontal cortex and hippocampus in AD brains was significantly decreased when compared with normal age matched non-demented individuals, supporting the hypothesis that AD brains are particularly vulnerable to complement-mediated neuronal death (Yang et al., 2000). |
Disease | AD is a neurodegenerative disease that causes changes in brain function. AD usually affects people over the age of 65 years, with a progressive decline in memory, thinking, language and learning capacity. Age is the strongest predictor for the development and progression of AD (Tanna, 2004). |
Prognosis | AD is incurable. It leads to death within an average of eight years after diagnosis, the last three of which are typically spent in an institution. |
Cytogenetics | The molecular mechanisms and hypotheses of AD can be incredibly complex. One of the key events leading to AD appears to be the formation of a peptide (protein) known as amyloid beta (beta amyloid, Aβ), which clusters into amyloid plaques (senile plaques) on the blood vessels and on the outside surface of neurons of the brain. This plaques have been shown to activate the complement system (Kolev et al., 2009). |
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Entity | Breast cancer |
Disease | Human breast cancer cells are protected from complement-dependent lysis (CDC) by overexpression of CD59 (Yu et al., 1999). It has been shown in numerous studies that inhibition/neutralization of CD59 on breast tumour cells increases tumour killing by complement system both in vivo and in vitro. |
Prognosis | A recent comparative proteomics study provided novel insights into key proteins associated with the metastatic potential of breast cancer cells and identified CD59 as a marker for breast cancer aggressiveness (Terp et al., 2012). |
Oncogenesis | Overexpression of CD59 on the surface of tumour cells confers resistance to CDC which has been suggested to result in tumour growth (Chen et al., 2000; Donev et al., 2006). |
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Entity | Ovarian cancer |
Disease | CD59 is strongly expressed in the ovarian tumor tissues and their associated cell lines cells in all 28 benign and malignant tumors examined (Bjørge et al., 1997). Neutralization of CD59 with an anti-CD59 monoclonal antibody or inhibition of cd59 expression by siRNA significantly enhances CDC of the ovarian cell lines (Kolev et al., 2011). |
Prognosis | Significant reduced levels of CD59 were detected in the urine of patients with ovarian carcinoma compared to the control subjects (Abdullah-Soheimi et al., 2010). Thus, CD59 can be used as a biomarker in the development of noninvasive assays for diagnosis and screening for ovarian carcinoma. |
Oncogenesis | It has been demonstrated that overexpression of CD59 on cancer cell surface promotes tumour growth in vitro and in vivo by protecting them from complement lysis (Chen et al., 2000; Donev et al., 2006). |
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Entity | Various cancers |
Note | Complement is one of the main mediators of antibody-based cancer therapy via the CDC effect. Tumour cells overexpress CD59 which plays a critical role in resistance to CDC and monoclonal antibody-therapy for treatment of cancer (Juhl et al., 1997; Yan et al., 2008). |
Disease | CD59 is overexpress on the surface of different tumour types and their associated cell lines - colorectal cancer (Thorsteinsson et al., 1998), B-cell leukemias (Treon et al., 2001), neuroblastoma (Donev et al., 2008), prostate cancer (Jarvis et al., 1997), malignant melanoma (Weichenthal et al., 1999), lung carcinoma (Varsano et al., 1998), etc. |
Prognosis | In general, overexpression of CD59 on tumour surface is associated with poor prognosis. |
Oncogenesis | It has been demonstrated that overexpression of CD59 on cell surface promotes tumour growth in vitro and in vivo by protecting them from complement lysis (Chen et al., 2000; Donev et al., 2006). |
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Entity | Diabetes |
Note | Glycation was shown to inhibit CD59 function. In presence of glycation on CD59 it loses its MAC-inhibitory function and results in vascular proliferavative complications like diabetes (Davies et al., 2005). Loss of functional CD59 in hyperglycaemics contributes to their susceptibility to lysis by complement. Thus, it was suggested that glycation-induced inactivation of CD59 is a factor contributing to anaemia in type I diabetes. It is hypothesized that glycation near residue K41 and W40, two highly conserved amino acids essential for the CD59 function, inhibits CD59 function (Davies et al., 2005). |
Disease | Diabetes is a disease due to an increased level in glucose, which results in glycation and impairment of protein function. Glycation is when a sugar molecule binds a protein or a lipid molecule without the control of an enzyme. |
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Entity | Age-related macular degeneration (AMD) |
Note | Immunohistochemical studies have localized activated complement components, including the membrane attack complex (MAC) in retinal pigment epithelium (RPE) and drusen in the eyes of patients with AMD (Johnson et al., 2000). CD59 protects autologous cell killing by preventing the formation of lytic MAC on the cell membrane (Meri et al., 1990). The expression of CD59 was found to be significantly lower on CD14(+) monocytes in patients with neovascular AMD compared with controls (Singh et al., 2012). Introduction of human CD59 using adenoviral vectors as a possible therapeutic strategy has been proposed (Ramo et al., 2008). |
Disease | Molecular basis for AMD is not well understood, a growing body of evidence has recently implicated inflammatory processes, specifically the complement system, in the pathogenesis of this disease (Johnson et al., 2000). |
Prognosis | AMD is the leading cause of blindness among the elderly in industrialized nations (Klein et al., 2008). |
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Entity | Major depression |
Note | Expression of CD59 has been found significantly inhibited in an animal model of major depression (Pajer et al., 2012). This suggests that neurons become more susceptible to complement-mediated damage. |
Disease | Early-onset major depressive disorder (MDD) is a serious psychiatric condition occurring in people under 25 years of age. Early onset of MDD predicts greater familial risk, suggesting a substantial genetic etiology. Approximately 1% of the population of 12 years has MDD, but rates increase to 17-25% by late adolescence and young adulthood (Pajer et al., 2012). |
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