الفهرس 
TitleOnly 14 pages are availabe for public view
 |  | from | 99 |  |  |
| | | from | 99 | | |
Abstract
T2DM is the most prevalent type accounting for 90% of DM. chronic hyperglycemia associated with diabetes can affect some organs like retina, kidneys, heart nerves, and blood vessels. DKD is the principal cause of CKD worldwide which is characterized by significant proteinuria and hyper-filtration, leading eventually to renal failure. Inflammation and oxidative stress have a central role in the pathogenesis of T2DM and also DKD. Activation of NLRP3 inflammasome induces maturation of procaspase-1 to become caspase-1, further inducing the secretion of IL-1β and IL-18 and inflammatory cell death termed pyroptosis. ASC plays a role in the assembly of inflammasomes where ASC aggregates formation is the hallmark of inflammasome activation.
Besides its role in innate immunity, ASC was found to be involved in adaptive immunity. IgA is the second most prevalent antibody in serum comprising 2 subtypes: IgA1 and IgA2. IgA levels are altered in some diseases like diabetes, but there is controversy if their levels are increased or decreased during T2DM. Moreover, little is known about if there is a relation between ASC and IgA levels and ratios during diabetes and DKD. So, in this study, we measured the ASC levels in all individuals and related them to serum IgA1, IgA2 levels, and IgA1/IgA2 ratio
The present study included a total of 45 individuals who were classified into group (1) that included 30 patients who were sub-classified into 15 diabetic patients without kidney disease (group 1A) and 15 patients with DKD (group 1B) as well as 15 age- and sex-matched healthy subjects were included as a control group (group 2). All subjects were examined for serum creatinine that was used for the calculation of eGFR, HbA1c, and albuminuria. ASC levels were measured using culture supernatant extracted after culturing of PBMCs by ELISA, but IgA1 and IgA2 were determined by ELISA using the serum.
Current results revealed that inflammasome adaptor protein (ASC) levels were significantly higher in DKD patients than diabetic and control groups (p1=0.001*, p3=0.046*, respectively). IgA1 levels were significantly lower in DKD patients than diabetic and control groups (p1=0.023*, p3=0.006*, respectively), but IgA2 levels and IgA1/IgA2 ratio showed no significant change in their levels in DKD patients (P=0.252, P=0.613, respectively).
Correlation studies showed that ASC levels were positively correlated with serum creatinine levels and albumin creatinine ratios (P=0.024*, P=0.001*, respectively) while negatively correlated with estimated glomerular filtration rate (P=0.012*). In addition, IgA2 levels were positively correlated with serum creatinine (p=0.024*) and negatively correlated with eGFR in DKD patients (p=0.035*). Moreover, ASC levels were negatively correlated with serum IgA1 levels in normal physiological conditions (p=0.035*).
In addition, age of patients was positively correlated with serum creatinine (p=0.029*) while showed a negative correlation with eGFR (p=0.002*). Also, the current study showed a significant positive correlation between duration of diabetes and HbA1c levels (p=0.001*)
Summary, Conclusion and Recommendations
50
6.2. Conclusion
The significant association of upregulated ASC levels with increased albuminuria and reduced eGFR in DKD patients may indicate the emerging role of inflammasome adaptor protein ASC in the persistence of chronic inflammation in DKD.
The decreased IgA1 levels in DKD patients may reflect their role in the pathogenesis of DKD.
The significant association of increased IgA2 levels with increased serum creatinine and reduced eGFR in DKD patients may reflect the role of therapeutic approaches concerning IgA subtypes to modulate DKD in the future.
No significant correlation was observed between ASC levels and IgA subtypes /ratio in patients.
6.4. Recommendation
Further studies on large sample size including severe cases of T2DM to evaluate relationship between ASC and IgA subtypes/ratio.
The measurement of total IgA of all cases and comparing their levels with those of ASC.
Measurement of IgA1, IgA2 and total IgA in renal tissues will give a more precise and valuable results.
Future studies to investigate the possibilities for clinical control of T2DM by modulating ASC and IgA subtypes.
Evaluate the potential role of inflammasome adaptor protein ASC in type 1 DM and other immunological disorders.