الفهرس 
Lupus NephritisOnly 14 pages are availabe for public view
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Abstract
Summary
SLE is not an uncommon disease, renal affection occurs in
more than 60% in patients with SLE, and around 15% of patients
with lupus nephritis progress to ESRD.
Lupus nephritis is a disease with poor clinic-pathological
correlation, and patients usually have ongoing immune mediated
renal pathology, without clinical manifestations.
The gold standard for diagnosis of lupus nephritis is renal
biopsy, but being invasive and not complications free, it cannot be
routinely done for proper assessment of the current state of
nephritis.
A reliable and non invasive tool is needed for proper
monitoring of lupus nephritis, to allow modification of drug dose
and duration of therapy based on the predicted outcome to
improve treatment efficacy and reduce toxicity.
Current laboratory markers of lupus nephritis such as anti
DNA titer, proteinuria, and complement levels are unsatisfactory
as they lack proper sensitivity and specificity toward renal
disease.
Recently, many novel biomarkers are being studied for
assessing their diagnostic accuracy to lupus nephritis, and their
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ability to predict not only renal pathology but also renal activity
to allow for early intervention.
Anti C1q antibodies, are auto antibodies which attack
complement fraction C1q. C1q is known to have a protective role
in lupus nephritis by enhancing clearance of immunogenic
apoptotic bodies.
Monocyte chemoattractant protein 1 (MCP-1) is a
chemokine which was found to rise markedly in the urine samples
of patients with lupus nephritis.
Both markers were found to have good correlation with the
degree of renal inflammation and the levels of traditional
biomarkers of activity.
In our study, we aimed at assessing the pattern of
expression and diagnostic performance of both markers in
patients with lupus nephritis and to highlight their renal flare
predictive ability.
We included 90 candidates recruited from Ain Shams
University hospitals Nephrology and Rheumatology clinics and
inpatient wards.
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130
Patients divided into 3 groups namely; Active lupus
nephritis proved by biopsy (n. 30), lupus nephritis in remission (n.
30), and healthy controls (n. 30)
All lupus nephritis patients were subjected to history
taking, clinical and laboratory assessment, including conventional
markers of lupus activity.
Patients with activity were followed up after 6 months
aiming at assessing AntiC1q and uMCP-1 levels after induction
immunotherapy. In addition, patients in remission were followed
up for 1 year and biomarkers were measured every 4 months
aiming at assessing their ability to predict renal flare if it
happened during the follow up period.
In the cross-sectional phase of our study both serum levels
anti C1q and urine levels of MCP-1 were higher in activity group
in comparison to patients in remission and to control group.
Anti C1q levels were found to be higher in patients with
class IV lupus nephritis than other classes, while MCP-1 levels
didn’t show any significant difference regarding lupus nephritis
class.
AntiC1q levels correlated significantly with clinical
assessment score SLEDAI, conventional biomarkers of renal
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131
activity (Proteinuria, Anti DNA titer, C3, C4, ESR) and with
activity index in renal biopsy.
uMCP-1 levels correlated significantly with clinical
assessment score SLEDAI, conventional biomarkers of renal
activity (Proteinuria, Anti DNA titer, C3, C4, ESR) and with
chronicity index in renal biopsy.
Based on the data obtained from patients in activity and in
remission, a receptor operator curve (ROC) analysis was done to
define cutoff level for each marker and study its diagnostic
performance in comparison to Anti DNA, C3, and C4.
AntiC1q antibodies level was superior to other biomarkers
with sensitivity 96.7%, specificity 70% at cut off level ≥ 26
IU/ml, while uMCP-1 levels had sensitivity of 73.3%, and
specificity 63.3%.
Patients in remission were followed up for a period of 1
year during levels of anti C1q and uMCP-1 were analyzed every 4
months. Five patients withdraw their consent and refused to
continue the follow up phase, 2 patients died with fatal
pneumonias, 23 patients completed their follow up, out of them 7
patients developed renal activity.
The pattern of the biomarkers were studied in 7 patients
who developed renal activity to assess whether any of the markers
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132
can predict renal flare. A marker is considered a predictor if its
level before renal flare exceeded its estimated cut off level from
phase I of the study. Out of 7 cases with renal flare during follow
up, Anti C1q titer predicted renal flare in 5 cases (71.4%), while
uMCP-1 predicted only 3 cases (42.8%).
Patients who developed renal flare were studied
individually. It was obvious that anti C1q is a more dynamic
marker than urinary MCP-1, being higher before renal activity in
most cases and then gets lower gradually after treatment, while
MCP-1 didn’t show any specific pattern upon which its predictive
ability can be validated.
30 patients in activity were followed after induction
immunotherapy, 2 patients died, the remaining 28 patients
showed a dramatic DROP in the AntiC1q level after induction of
remission, while uMCP-1 levels didn’t show significant change.
In conclusion, both markers show significant increase in
levels in cases of activity with good correlation with clinical and
laboratory parameters of activity. Anti C1q is a more sensitive
and specific marker than MCP-1 and other conventional
biomarkers in identifying renal activity, even more its level was
higher with more proliferative renal pathology. AntiC1q is more
dynamic biomarker than MCP-1 and its levels can forecast renal
activity and can be used in assessment of response to treatment.
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133
uMCP-1 levels are affected by the chronicity of the renal disease
and to the degree if renal fibrosis and its levels are not reliable
alone in assessing renal activity, and cannot be used for follow up
of response to treatment.