الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 119 |  |  |
| | | from | 119 | | |
Abstract
Primary immune thrombocytopenia (ITP) is one of the common causes of thrombocytopenia in otherwise asymptomatic adult. ITP may occur in isolation (primary) or in association with other disorders (secondary).
Pathogenesis of immune thrombocytopenia is a complex disorder of immune dysregulation; however, the final pathway is loss of tolerance of the immune system to self-antigens located on the surface of the platelets and megakaryocyte. There are different roles of both T and B cells that have been speculated to play in the development of immune thrombocytopenia.
The mainstay of treatment is glucocorticoids. Resistance to glucocorticoid therapy has become a major barrier in effectively treating patients with inflammatory diseases including ITP. Glucocorticoids signal through the glucocorticoid receptor (GR), a member of the superfamily of nuclear receptors, in almost every tissue in the human body.
GR is the product of a single gene, Nuclear Receptor Subfamily 3(NR3C1), that undergoes alternative processing to yield multiple, functionally distinct subtypes of GR. Alternative splicing of GR generates hGRα and hGRβ isoforms. The hGRα isoform binds to glucocorticoids, translocates to the nucleus, and recruits coregulators to exert transcriptional effects. Low or high expressions of this isoforms have been associated with GC resistance.
This research set out to determine the expression of GRα m RNA isoform in adult ITP and its relation with glucocorticoid resistance and included GRp, GRγ and GRβ isoforms.
Cases were selected from Alexandria University Main Hospital, then divided into two groups. First group consisted of 35 patients already diagnosed as ITP or newly diagnosed ITP patients. This was further categorized into the glucocorticoid-sensitive and glucocorticoid-resistant .The second group consisted of 15 healthy volunteers.
RNA was then extracted and the samples collected were stored at -80 degrees then Real time PCR was done.
The results were as follows.
The age of the patients ranged from a minimum of 17- 65 years with a mean of 35.4+/- 11.9 whereas in the control group it ranged from 27-50 years with a mean of 31.7+/-5.8.There was no statistical significance regarding age between the two groups(P=0.161).
Regarding sex the females accounted for 84%(28 females) of the patients while males were only 15.2%(5 males) whereas in the controls the females were 46.7% and males 53.3%.There was a statistical significance between the two groups regarding gender.(P=0.019)
The medians(min-max) of the steroid sensitive groups for GR α, P, β γ and α/ β ratio were 109.7(3.9-579.8),6.9(0.1-44.4), 0.002(0.0-0.003), 0.4(0.01-11.1),47472(8.4-200000) respectively and that of steroid resistant groups were 3.9(1.7-101.1), 0.02(0.01-2.3), 0.006(0.002-0.1), 0.03(0.003-2.2), 224.5(0.9-53090) respectively while that of the controls were 7.2(3.9-8.2),0.5(0.3-0.9),4.5(3.2-6.1),0.01(0.004-0.02),1.4(1.0-2.0) also respectively
There was a statistical significance for GR β (KWX2=18.275, P<0.0001*) and GR α/β ratio (KWX2=9.282, P=0.01*)
Between the isoforms themselves GRα has a strong positive correlation with GR p, γ and the ratio of GRα/β which was statistically significant(r=0.807, p=0.0001. r=0.811, p= 0.0001.r=0.982, p=0.0001 respectively). It is also inversely correlating with GRβ strongly and is statistically significant as well(r=-0.859, p=0.0001).
GRP showed strong positive correlation with GRγ and GRα/β ratio which is statistically significant (0.705, p=0.005. r=0.793, p=0.001 respectively). It showed a moderate negative correlation with GRβ which was also significant(r= -0.565, p=0.035).
In study we found out that ITP affected more females than males. With regards to age it affects both sexes equally and age is not an influencing factor in terms of GC response.
We also found out that that high expression of GRβ and low expression of GRα/β ratio may be associated with GR resistance but GRα,p and γ showed statistical significance between sensitive and resistant groups
GRα and GR β inversely correlated among our patients hence possible explanation for GRβ acting as an inhibitor of GRα.
We recommended that more of such research to be done because there is still a lot of conflicting information as to whether low or high expressions of the isoforms is associated with GC sensitivity or not. Also very little research on GRγ and GRp isoforms hence more need to be done. More correlation studies between the isoforms should be encouraged. Studies on the accuracy of the isoforms in assessing GR sensitivity should also be encouraged.