الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease
characterized by a wide range of clinical and serological manifestations. Lupus nephritis
(LN) is a common complication associated with poor outcome.
Vitamin D is a steroid hormone which has multiple effects on host immune response.
It counteracts T-cell proliferation and maturation as well as inhibits B-cell differentiation.
In addition, it was shown that low level of vitamin D is correlated with the clinical
manifestations of LN.
Cyclin dependent kinase-1 (CDK-1) is a member of the cyclin-dependent protein
kinases that regulate cell cycle. Recently, there is an emerging clue that CDK-1 which
positively regulate type I IFN, acts as key regulator of SLE and lupus nephritis
pathogenesis.
In this study we aimed to determine the relation between vitamin D level and cyclin
dependent kinase-1 (CDK-1) gene expression in Lupus nephritis patients and their impact
on disease activity.
We used ELISA technique to measure vitamin D level and autoantibodies (ANA,
anti-ds-DNA). Nephlometry was used to measure complement components (C3, C4).
CDK-1 gene expression assessed from cultures of PBMCs with and without CDK-1
inhibitor (RO-3306) by real time PCR.
Our study included thirty five subjects, ten of them were healthy subjects and twenty
five were LN patients defined by SLICC classification criteria. There were 8 patients with
moderate disease activity and 17 were of high disease activity according to the SLEDAI.
All patients enrolled in this study had at least 8 points of renal SLEDAI system.
Our study showed that there was a statistical significant anemia, lymphopenia,
thrombocytopenia in LN patients in comparison to controls. Also, there was a statistical
significant increase in urinary casts, urinary albumin/ creatinine ratio, proteinuria, serum
creatinine and blood urea with statistical significant decrease in eGFR, as well as there
were statistical significant increased titer of both ANA, anti-ds-DNA and statistical
significant decrease of complement components C3, C4 in LN patients in comparison to
controls. Additionally, the levels of inflammatory markers (ESR and CRP) were
statistically significantly higher in patients in comparison to controls.
Vitamin D levels in our study were categorized into the three levels (severe
deficiency, insufficient, optimal) and insufficient level was a predominant level in patients
included in our work followed by severe deficiency and then optimal.
Vitamin D showed statistical significant decreased in LN patients in comparison to
control group. Moreover correlation analysis of our study clarified that there was a
statistical significant negative correlation between vitamin D and immunological
parameters such as ANA, anti-ds-DNA, CRP.
Summary & Conclusions
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In addition, there was non-significant negative correlations between vitamin D level
and three clinical scoring systems, hematological parameters, urinary parameters (albumin/
creatinine ratio, proteinuria) and complements components C3, C4 as well as there were
non-significant positive correlations between vitamin D level and renal function tests
(serum creatinine, blood urea and eGFR).
In the present study, it was found that expression of CDK-1 was down-regulated in
majority of LN patients. Furthermore correlation analysis of our study demonstrated a nonsignificant
negative correlation between CDK-1 gene expression and vitamin D level
before RO-3306 addition. However a non-significant positive correlation was found after
RO-3306 addition.
Also there were non-significant positive correlations between CDK-1 expression
(before and after RO-3306 addition) and three clinical scoring systems, hematological
parameters, proteinuria, serum creatinine and ESR. Moreover there was non-significant
negative correlation between CDK-1 gene expression (after and before RO-3306 addition)
and both of eGFR and complements components C3, C4.
Another correlation analysis clarify that there was a statistical significant positive
correlation between CDK-1 gene expression and urinary albumin/ creatinine ratio before
RO-3306 addition. However a non-significant positive correlation was found after RO-
3306 addition.
Finally, there was statistical significant positive correlation between CDK-1 gene
expression and both ANA and CRP before RO-3306 addition. Moreover a non-significant
positive correlation was found after RO-3306 addition.
We can conclude from that:-
Vitamin D deficiency acts as a potential risk factor for developing of SLE severity
and aggravated its clinical consequences especially lupus nephritis.
Deficiency of vitamin D level is may correlated with the inflammation and organdamage
mediated by immune complexes deposition in LN.
Due to immunomodulatory effects of vitamin D on innate and adaptive immune
responses, it may have promise as a potential prophylactic and therapeutic strategies
for LN and other autoimmune diseases.
CDK-1 gene is associated with different parameters of LN disease particularly with
renal indices, inflammatory markers and autoantibodies production. So targeting this
gene may provide presage tool to reduce the activity of disease.
Vitamin D level may effect on expression of CDK-1 gene in SLE patients foremost
with those who have LN.