EXPRESSION OF GLUCOCORTICOID RECEPTOR ISOFORMS (A, Β, Γ, AND P) IN ADULT EGYPTIAN PRIMARY IMMUNE THROMBOCYTOPENIA PATIENTS
(Abstract release date: 05/19/16)
EHA Library. El-defrawy M. 06/09/16; 132970; E1421
Prof. Dr. Mohamed El-defrawy
Contributions
Contributions
Abstract
Abstract: E1421
Type: Eposter Presentation
Background
Glucocorticoid (GC) resistance has been demonstrated in nearly 30% of primary immune thrombocytopenia (ITP) patients even managed with high dosages GC. The biological effects of GC are mainly mediated through activation of glucocorticoid receptors (GR). An insight into the molecular mechanisms underlying GC resistance is important to avoid GC treatment in patients contraindicated from steroid use.
Aims
We aimed at determining glucocorticoid receptor (GR) isoforms expression in adult ITP and its relation to glucocorticoid resistance.
Methods
Thirty three ITP patients from the Hematology unit, Alexandria Main University Hospital were the subject of the study. They were subdivided into two groups (sensitive and resistant) according to their response to 4 weeks GC treatment. 15 healthy volunteers of matched age were also included. Glucocorticoid Receptor α, β, γ and p gene expression were measured in cases and controls by real time Polymerase Chain Reaction. (QIAamp® RNA blood mini kit (cat no. 52304). Informed written consent was obtained from allpatients and the study was approved by theMedical Ethical Committee.
Results
The mean age value of glucocorticoids sensitive (GCS), glucocorticoid resistant (GCR) and control group was 33.4±11.6, 38.1±12.3 and 31.7±5.8 years respectively (F=1.496, p=0.235). Half of our female patients (n=14) were GC resistant while all the males (n=5) were GC sensitive. Statistically significant difference between GR alpha mRNA isoform and GRa/ GRβ ratio was detected between GC resistant and GC responsive group while GRp, GRγ and GRβ were insignificantly differed between groups. GRα is expressed in most human tissues and cell line. It functions as ligand-dependent transcription factors. There is a wide variability in median value of GRα between our GCS and GCR patients. The ratio of GRα/GRβ expression is critical to the glucocorticoid responsiveness of various cells. Higher ratios correlate with glucocorticoid sensitivity, while lower ratios correlate with glucocorticoid resistance. There was non-statistically significant correlation between GR α and age (r=-0.302, p= 0.087). GRα had a strong inverse correlation with GRβ and a significant direct correlation with GRγ and p. Fig. 1 shows ROC curve of different GR isoforms in predicting GC resistance in ITP. GRα/β ratio had the highest sensitivity (81.8%) and is the most accurate predictor of GC resistance (79.2%). GRγ had the highest specificity (86.7%). GRβ had the lowest sensitivity (9.1%) and the lowest specificity (26.7%).
Conclusion
In this study, we noted a statistical significant difference between GR alpha mRNA isoform and GRa/ GRβ ratio within ITP patients. GRa and GRa/ GRβ were higher among GC sensitive compared to GC resistant groups. GRα/β ratio had the highest sensitivity (81.8%) and is the most accurate predictor of GC resistance (79.2%). We concluded that the study of GRa and GRa/ GRβ ratio is recommended early in ITP assessment to avoid unnecessary glucocorticoids side effects during treatment.
Session topic: E-poster
Keyword(s): Corticosteroids, Idiopathic thombocytopenic purpura (ITP), Platelet, Resistance
Type: Eposter Presentation
Background
Glucocorticoid (GC) resistance has been demonstrated in nearly 30% of primary immune thrombocytopenia (ITP) patients even managed with high dosages GC. The biological effects of GC are mainly mediated through activation of glucocorticoid receptors (GR). An insight into the molecular mechanisms underlying GC resistance is important to avoid GC treatment in patients contraindicated from steroid use.
Aims
We aimed at determining glucocorticoid receptor (GR) isoforms expression in adult ITP and its relation to glucocorticoid resistance.
Methods
Thirty three ITP patients from the Hematology unit, Alexandria Main University Hospital were the subject of the study. They were subdivided into two groups (sensitive and resistant) according to their response to 4 weeks GC treatment. 15 healthy volunteers of matched age were also included. Glucocorticoid Receptor α, β, γ and p gene expression were measured in cases and controls by real time Polymerase Chain Reaction. (QIAamp® RNA blood mini kit (cat no. 52304). Informed written consent was obtained from allpatients and the study was approved by theMedical Ethical Committee.
Results
The mean age value of glucocorticoids sensitive (GCS), glucocorticoid resistant (GCR) and control group was 33.4±11.6, 38.1±12.3 and 31.7±5.8 years respectively (F=1.496, p=0.235). Half of our female patients (n=14) were GC resistant while all the males (n=5) were GC sensitive. Statistically significant difference between GR alpha mRNA isoform and GRa/ GRβ ratio was detected between GC resistant and GC responsive group while GRp, GRγ and GRβ were insignificantly differed between groups. GRα is expressed in most human tissues and cell line. It functions as ligand-dependent transcription factors. There is a wide variability in median value of GRα between our GCS and GCR patients. The ratio of GRα/GRβ expression is critical to the glucocorticoid responsiveness of various cells. Higher ratios correlate with glucocorticoid sensitivity, while lower ratios correlate with glucocorticoid resistance. There was non-statistically significant correlation between GR α and age (r=-0.302, p= 0.087). GRα had a strong inverse correlation with GRβ and a significant direct correlation with GRγ and p. Fig. 1 shows ROC curve of different GR isoforms in predicting GC resistance in ITP. GRα/β ratio had the highest sensitivity (81.8%) and is the most accurate predictor of GC resistance (79.2%). GRγ had the highest specificity (86.7%). GRβ had the lowest sensitivity (9.1%) and the lowest specificity (26.7%).
Conclusion
In this study, we noted a statistical significant difference between GR alpha mRNA isoform and GRa/ GRβ ratio within ITP patients. GRa and GRa/ GRβ were higher among GC sensitive compared to GC resistant groups. GRα/β ratio had the highest sensitivity (81.8%) and is the most accurate predictor of GC resistance (79.2%). We concluded that the study of GRa and GRa/ GRβ ratio is recommended early in ITP assessment to avoid unnecessary glucocorticoids side effects during treatment.
Session topic: E-poster
Keyword(s): Corticosteroids, Idiopathic thombocytopenic purpura (ITP), Platelet, Resistance
Abstract: E1421
Type: Eposter Presentation
Background
Glucocorticoid (GC) resistance has been demonstrated in nearly 30% of primary immune thrombocytopenia (ITP) patients even managed with high dosages GC. The biological effects of GC are mainly mediated through activation of glucocorticoid receptors (GR). An insight into the molecular mechanisms underlying GC resistance is important to avoid GC treatment in patients contraindicated from steroid use.
Aims
We aimed at determining glucocorticoid receptor (GR) isoforms expression in adult ITP and its relation to glucocorticoid resistance.
Methods
Thirty three ITP patients from the Hematology unit, Alexandria Main University Hospital were the subject of the study. They were subdivided into two groups (sensitive and resistant) according to their response to 4 weeks GC treatment. 15 healthy volunteers of matched age were also included. Glucocorticoid Receptor α, β, γ and p gene expression were measured in cases and controls by real time Polymerase Chain Reaction. (QIAamp® RNA blood mini kit (cat no. 52304). Informed written consent was obtained from allpatients and the study was approved by theMedical Ethical Committee.
Results
The mean age value of glucocorticoids sensitive (GCS), glucocorticoid resistant (GCR) and control group was 33.4±11.6, 38.1±12.3 and 31.7±5.8 years respectively (F=1.496, p=0.235). Half of our female patients (n=14) were GC resistant while all the males (n=5) were GC sensitive. Statistically significant difference between GR alpha mRNA isoform and GRa/ GRβ ratio was detected between GC resistant and GC responsive group while GRp, GRγ and GRβ were insignificantly differed between groups. GRα is expressed in most human tissues and cell line. It functions as ligand-dependent transcription factors. There is a wide variability in median value of GRα between our GCS and GCR patients. The ratio of GRα/GRβ expression is critical to the glucocorticoid responsiveness of various cells. Higher ratios correlate with glucocorticoid sensitivity, while lower ratios correlate with glucocorticoid resistance. There was non-statistically significant correlation between GR α and age (r=-0.302, p= 0.087). GRα had a strong inverse correlation with GRβ and a significant direct correlation with GRγ and p. Fig. 1 shows ROC curve of different GR isoforms in predicting GC resistance in ITP. GRα/β ratio had the highest sensitivity (81.8%) and is the most accurate predictor of GC resistance (79.2%). GRγ had the highest specificity (86.7%). GRβ had the lowest sensitivity (9.1%) and the lowest specificity (26.7%).
Conclusion
In this study, we noted a statistical significant difference between GR alpha mRNA isoform and GRa/ GRβ ratio within ITP patients. GRa and GRa/ GRβ were higher among GC sensitive compared to GC resistant groups. GRα/β ratio had the highest sensitivity (81.8%) and is the most accurate predictor of GC resistance (79.2%). We concluded that the study of GRa and GRa/ GRβ ratio is recommended early in ITP assessment to avoid unnecessary glucocorticoids side effects during treatment.
Session topic: E-poster
Keyword(s): Corticosteroids, Idiopathic thombocytopenic purpura (ITP), Platelet, Resistance
Type: Eposter Presentation
Background
Glucocorticoid (GC) resistance has been demonstrated in nearly 30% of primary immune thrombocytopenia (ITP) patients even managed with high dosages GC. The biological effects of GC are mainly mediated through activation of glucocorticoid receptors (GR). An insight into the molecular mechanisms underlying GC resistance is important to avoid GC treatment in patients contraindicated from steroid use.
Aims
We aimed at determining glucocorticoid receptor (GR) isoforms expression in adult ITP and its relation to glucocorticoid resistance.
Methods
Thirty three ITP patients from the Hematology unit, Alexandria Main University Hospital were the subject of the study. They were subdivided into two groups (sensitive and resistant) according to their response to 4 weeks GC treatment. 15 healthy volunteers of matched age were also included. Glucocorticoid Receptor α, β, γ and p gene expression were measured in cases and controls by real time Polymerase Chain Reaction. (QIAamp® RNA blood mini kit (cat no. 52304). Informed written consent was obtained from allpatients and the study was approved by theMedical Ethical Committee.
Results
The mean age value of glucocorticoids sensitive (GCS), glucocorticoid resistant (GCR) and control group was 33.4±11.6, 38.1±12.3 and 31.7±5.8 years respectively (F=1.496, p=0.235). Half of our female patients (n=14) were GC resistant while all the males (n=5) were GC sensitive. Statistically significant difference between GR alpha mRNA isoform and GRa/ GRβ ratio was detected between GC resistant and GC responsive group while GRp, GRγ and GRβ were insignificantly differed between groups. GRα is expressed in most human tissues and cell line. It functions as ligand-dependent transcription factors. There is a wide variability in median value of GRα between our GCS and GCR patients. The ratio of GRα/GRβ expression is critical to the glucocorticoid responsiveness of various cells. Higher ratios correlate with glucocorticoid sensitivity, while lower ratios correlate with glucocorticoid resistance. There was non-statistically significant correlation between GR α and age (r=-0.302, p= 0.087). GRα had a strong inverse correlation with GRβ and a significant direct correlation with GRγ and p. Fig. 1 shows ROC curve of different GR isoforms in predicting GC resistance in ITP. GRα/β ratio had the highest sensitivity (81.8%) and is the most accurate predictor of GC resistance (79.2%). GRγ had the highest specificity (86.7%). GRβ had the lowest sensitivity (9.1%) and the lowest specificity (26.7%).
Conclusion
In this study, we noted a statistical significant difference between GR alpha mRNA isoform and GRa/ GRβ ratio within ITP patients. GRa and GRa/ GRβ were higher among GC sensitive compared to GC resistant groups. GRα/β ratio had the highest sensitivity (81.8%) and is the most accurate predictor of GC resistance (79.2%). We concluded that the study of GRa and GRa/ GRβ ratio is recommended early in ITP assessment to avoid unnecessary glucocorticoids side effects during treatment.
Session topic: E-poster
Keyword(s): Corticosteroids, Idiopathic thombocytopenic purpura (ITP), Platelet, Resistance
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