Lupus (2017) 0, 1–11

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PAPER

Interferon alpha gene expression and serum level association with

low vitamin D levels in Egyptian female patients with systemic
lupus erythematosus
Sahar M Abdel Galil1,4, Abeer M El-Shafey1, Rehab S Abdul-Maksoud2 and Mohamed El-Boshy3
1
Rheumatology and Rehabilitation Department, Faculty of Medicine, Zagazig University, Egypt; 2Medical Biochemistry Department, Faculty of
Medicine, Zagazig University, Egypt; 3Department of Laboratory Medicine, Faculty of Applied Medical Science, Umm Al-Qura University,
Makkah, Kingdom of Saudi Arabia; and 4Medicine Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia

Background: Patients with systemic lupus erythematosus (SLE) are prone to develop vitamin
D (25(OH) D3) deficiency, due to several factors and there is an association between lower
vitamin D levels and higher SLE disease activity. The aim of this research was to assess the
prevalence of vitamin D deficiency in Egyptian female patients with SLE. Furthermore, we
analyzed the potential relationship between this deficiency and SLE manifestations, disease
activity, and its effect on interferon alpha (IFN-a) gene expression and serum level. Methods:
We evaluated the serum levels of vitamin D 25(OH)D3 and IFN-a by enzyme-linked immuno-
sorbent assay (ELISA). IFN-a gene expression was measured by real-time polymerase chain
reaction (PCR) assay in 123 Egyptian female patients with SLE and in 100 females as a healthy
control group. Results: Vitamin D deficiency was prevalent in 20.30%, while insufficiency was
prevalent in 42.40% of the total group of patients. Serum levels of 25(OH)D3 were signifi-
cantly decreased in the group of severe disease, and in the group of patients with lupus
nephritis. 25(OH)D3 showed highly significant negative correlation with the SLE Disease
Activity Index (SLEDAI) in the high activity group and lupus nephritis group. There was a
significant negative correlation between 25(OH)D3 and IFN-a serum level and gene expres-
sion in all patients; more significant in the group with lupus nephritis. Conclusions: The
deficiency of 25(OH)D3 has a direct relationship with increase disease activity and nephritis
in Egyptian SLE patients, suggesting the need for vitamin D supplementation in these
patients. Also, it is directly correlated with increased secretion and gene expression of IFN-
a, suggesting its role in pathogenesis of lupus nephritis, to be confirmed by further longitu-
dinal observational studies. Lupus (2017) 0, 1–11.

Key words: SLE; IFN-a; vitamin D; 25(OH)D3; disease activity; nephritis

Introduction from infants to geriatric patients.2 SLE often pre-

sents with renal involvement, with up to 10–60% of
Systemic lupus erythematosus (SLE) is an idio- patients with lupus nephritis ultimately developing
pathic connective tissue disease, characterized by end-stage renal disease.3
the production of autoantibodies which leads to Although the primary function of vitamin D is
immune complex deposition, inflammation, and the regulation of bone mineral homeostasis, several
eventually, permanent organ damage.1 data showed it as an immunosuppressive hormone
It commonly affects women of childbearing age and a regulator of the immune system.4 Vitamin D
with female: male ratio of approximately 6–10:1, receptors were found in most cells of both the
with a peak incidence between the ages of 15 and innate and the adaptive immune system, including
40 years. However, SLE can affect all age groups, macrophages, dendritic cells, B-cells and T-cells.5
Since this discovery, the concept that vitamin D
has roles in the regulation of the immune response
Correspondence to: Sahar M Abdel Galil, Faculty of Medicine,
Zagazig University, 44519 Egypt.
has emerged.6 It has been reported that 1,25-
Email: dr_saharmahfouz@yahoo.com dihydroxy vitamin D3 (24(OH)D3) inhibits inter-
Received 13 February 2017; accepted 23 May 2017 feron (IFN)-c secretion by Th1 cells, negatively
! The Author(s), 2017. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203317716321
 IFN-a gene expression in SLE patients
SM Abdel Galil et al.
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regulates interleukin-12 (IL-12) production by Subjects and methods

down-regulation of nuclear factor (NF)-kB, inhi-
bits IL-2 and granulocyte-macrophage colony- Participants
stimulating factor, as well as in lymphocyte
proliferation.7,8 This cross-sectional study included 123 Egyptian
Vitamin D inhibits the adaptive immune female patients with SLE and 100 age matched
response and may suppress the cytokines involved females as healthy controls. The control group
in the physiopathology of SLE. It plays an import- reported no history of autoimmune disease and
ant role in the inhibition of dendritic cell matur- they were from similar geographical areas as the
ation, Th1 activity, B-cell maturation and patients. SLE patients were diagnosed by being
differentiation and Treg cell function.9 Previously, fulfilling more than four of the American College
it was documented that there is an association of Rheumatology revised classification criteria
between lower vitamin D levels and higher SLE for SLE.25
disease activity.10–12 The problem of vitamin D Patients were recruited from inpatient sections
deficiency/insufficiency in Egyptian patients with and outpatient clinics of Rheumatology & The
SLE seems to be common in both juvenile-onset Rehabilitation Department of Zagazig University
SLE and adult patients.13 Patients with SLE are Hospitals, Zagazig, Egypt.
prone to developing vitamin D deficiency, due to The present study was approved by the Research
several factors such as avoidance of sunshine due to Ethics Committee of Zagazig University Hospitals,
photosensitivity,14 sunscreen usage,15 chronic renal and all participants provided written informed con-
insufficiency,16 some medications such as cortico- sent prior to study enrollment.
steroids17 and antimalarials.18 All participants were nonsmokers and did not
IFN-a is a pleiotropic cytokine affecting multiple receive vitamin D or calcium supplementation.
cell types involved in pathogenesis of systemic Patients were subjected to complete history taking
lupus. It can dramatically affect the development, and general examination for the presenting clinical
progression, and pathogenesis of SLE by affecting manifestations, which were defined as either present
the function and activation state of most major or absent according to the definitions in the SLE
immune cell subsets, thus acting as a bridge classification criteria. According to the presence of
between innate and adaptive immunity.19 nephritis, our patients were classified into two
Moreover, IFN-a causes myeloid dendritic cells groups, with and without nephritis. Disease activity
from lupus patients to phagocytose and present was assessed using the SLE Disease Activity Index
self-antigens to T-cells in a stimulatory, rather (SLEDAI-2K).26 Activity categories have been
than a regulatory manner.20 Such a process leads defined on the basis of SLEDAI scores: no activity
to loss of T-cell tolerance to self-antigens with sub- (SLEDAI ¼ 0), mild activity (SLEDAI ¼ 1–5),
sequent autoimmunity. IFN-a can prevent apop- moderate activity (SLEDAI ¼ 6–10), high activity
tosis and enhance proliferation of primary B-cells, (SLEDAI ¼ 11–19) and very high activity
the main cell of humoral autoimmunity in SLE, (SLEDAI  20).27 Accordingly, our study popula-
even in the absence of mitogenic stimuli.21 tion was also divided into three groups; mild, mod-
The major source of IFN-a in SLE patients are erate and high activity groups.
activated dendritic cell (DCs), and vitamin D3 has Serum vitamin D levels, serum IFN-a levels and
been shown to inhibit maturation/activation of gene expression were compared between all study
DCs and expression of IFN-a induced genes in populations, and correlated with the clinical mani-
SLE patients.22,23 Thus, vitamin D is considered festations and SLEDAI-2K scores of the disease in
to have an immunomodulating effects that result all patient groups.
in an increase or decrease in the levels of pro- and
anti-inflammatory cytokines, which may, in turn, Laboratory investigations
alter the course of SLE, influencing disease activity
and chronicity.24 Blood samples were collected from all participants.
In the present work, we have tried to determine A total of 3 ml of blood was left to clot for 30 min
the prevalence of vitamin D deficiency/insufficiency at room temperature before centrifugation and sera
in Egyptian females with SLE. Also, we tried to were separated and frozen at 20 C until analysis.
highlight the effect of low vitamin D on IFN-a Urine samples were collected from the patient
gene expression and serum level through its rela- groups. The following laboratory investigations
tionship with disease activity and its association were performed on the patient groups; erythrocyte
with clinical manifestations of the disease. sedimentation rate (ESR), urinalysis and 24-hour
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 IFN-a gene expression in SLE patients
SM Abdel Galil et al.
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urine protein, blood urea, serum creatinine and 10 pmol of each primer. The cycling conditions
serum complement components C3 and C4. Anti- were as follows: 95 C for 4 min; 35 cycles of 95 C
double stranded DNA (anti-ds-DNA) antibodies for 30 s, 55 C for 30 s and 72 C for 30 s. A final
were estimated using enzyme-linked immunosorb- elongation step was performed at 72 C for
ent assay (ELISA) (Immulisa, Immco Diagnostic, 10 min. Each measurement was performed in dupli-
NY, USA) according to the manufacturer’s cate. Melting curves were performed to confirm the
protocol. specificity of PCR products. IFN-a gene expression
was calculated using the 2-
Ct method where
Measurement of serum vitamin D and IFN-
Ct ¼ Ct of IFN-a -Ct of GAPDH.32
concentrations
Statistical analysis
Serum 25(OH)D3 level is the best indicator of over-
all vitamin D status, because it reflects total vitamin All statistical analyses were performed with SPSS,
D from dietary intake and sunlight exposure, as version 21.0 (IBM Corp, NY, USA).
well as the conversion of vitamin D from stores in The normality of continuous variables was estab-
the liver.28 Therefore, serum 25(OH)D3 levels were lished by means of the Kolmogorov–Smirnov test.
measured by a competitive ELISA (kit provided by Normally distributed variables were summarized
Immundiagnostik, USA). Values of 25(OH)D3  using the mean and standard deviation (SD). The
20 ng/ml were considered ‘deficient’; values ranging median and interquartile ranges (IQR) were used
from 21–29 ng/ml were considered ‘insufficient’ and for asymmetrically distributed variables. The
levels 30 ng/ml were considered ‘sufficient’.29 prevalence of vitamin D insufficiency and deficiency
Serum levels of IFN-a were measured using a was calculated as the ratio between the number of
human IFN-a ELISA kit (Bender MedSystems, patients with 25(OH)D3. The comparison of con-
CA, USA) according to the manufacturer’s instruc- tinuous variables of mild, moderate and severe dis-
tions with some modifications. Mouse serum at 5% ease groups were analyzed by means of one-way
was added to the assay buffer to neutralize hetero- analysis of variance and Kruskal–Wallis test of
trophile antibodies and avoid false-positive parametric and non-parametric data respectively.
results.30 Comparisons of continuous variables between
active and inactive lupus nephritis groups were
RNA extraction and reverse transcription done using the independent Student’s t-test in the
case of normal variables and the Mann–Whitney
Total RNA was isolated from whole blood using U-test in the case of non-normal variables. The
QIAamp RNA blood mini kit (Qiagen, CA, USA) results were considered significant at p < 0.05.
according to the manufacturer’s protocol. RNA Spearman correlation coefficients were used to
concentration was determined spectrophotometric- evaluate the association between 25(OH)D3,
ally at 260 nm and stored at 80 C. RNA was IFN-a and SLEDAI-2K.
reverse transcribed using QuantiTect reverse tran-
scription kit (Qiagen) according to the manufac-
turer’s instructions. Results
Real-time PCR assay of IFN-
Prevalence of 25(OH)D3 in SLE patients
The expression of IFN-a was carried out using real-
time thermal cycler (MJ Research Inc, Watertown, The demographic characteristics of the 123 SLE
Massachusetts, USA) according to Palmer et al.31 female patients included in this study are summar-
Glyceraldehyde-3 phosphate dehydrogenase ized in Table 1. The mean level of serum 25(OH)D3
(G3PDH) was used as internal control for data nor- was 25.96  8.21 ng/ml in all of our SLE patients.
malization. Primers used for PCR were as follow: A total of 52 of those patients (42.30%) had
IFN-a (sense: 50 TTCCTCCTGYYTGAWGGAC 25(OH)D3 insufficiency while 25 (20.30%) had
AGA-3; antisense: 50 -GATCTCATGATTTCTGC 25(OH)D3 deficiencies.
TCTGACA-30 ), G3PDH (sense: 50 -GGTATCGT
GGAAGGACTCATGAC-30 ; antisense: 50 -ATGC Characterization of patients according to
disease severity
CAGTGAGCTTCCCGTTCAGC-30 ). Real-time
PCR was performed in a total volume of 20 ml Demographic and clinical data (in different groups
containing: 2 ml of cDNA, 10 ml of Syber Green of patients) associated with disease severity are dis-
PCR Master Mix (Roche Diagnostics USA) and played in Table 1. Patient ages and disease duration
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Table 1 Demographic, clinical and laboratory characteristic Table 2 Demographic, clinical and laboratory characteristic
data for all study patients data (mean  SD) between different groups of patients by
disease activity
Variable SLE (n ¼ 123) Control (n ¼ 100)
Mild Moderate High
Age year (mean  SD) 38.34  9.38 36.24  7.54 activity activity activity
Disease duration year 7.31  4.04 NA Groups n ¼ 60 n ¼ 42 n ¼ 21
(mean  SD)
SLEDAI-2K (mean  SD) 6.54  3.84 NA Age (year) 38.70  9.48a 38.19  9.90a 40.52  8.23a
C3 mg/dl (mean  SD) 47.08  15.90 125.25  25.24 Disease duration (year) 6.52  3.48a 6.81  4.58a 7.52  4.09a
C4 mg/dl (mean  SD) 19.67  7.55 45.25  12.45 SLEDAI-2K score 3.87  2.04a 6.98  1.28b 13.48  1.47c
ESR mm/hr (median  IQR) 47.16  21.00 9.51  2.1 C3 (mg/dl) 50.08  11.14a 41.47  11.45b 26.85  6.93c
Positive anti-ds-DNA, n (%) 85 (69) NA C4 (mg/dl) 22.51  6.36a 20.72  6.252a 9.43  1.94b
Anti-ds-DNA U/ml 455  221 NA Creatinine (mg/dl) 1.21  0.248b 1.25  0.241b 1.76  0.261a
(median  IQR) Urea (mg/dl) 45.65  6.06b 49.47  8.90b 58.81  8.55a
Serum creatinine mg/dl 1.32  0.33 0.95 ESR (mm/hr) 35.85  11.54c 50.36  8.57b 97.42  14.29a
(mean  SD) Anti-ds-DNA (U/ml)
Urea mg/dl (mean  SD) 49.21  8.84 29.5  5.1 Median  IQR 395  92.75c 567  170b 865  122a
Malar rash, n (%) 97 (81) NA 25(OH)D3 (ng/ml) 29.25  6.74a 27.30  5.80b 13.85  3.69c
Discoid rash, n (%) 20 (16) NA 25(OH)D3 28 (46.6) 21 (50) 3 (14.3)
Photosensitivity, n (%) 71 (58) NA insufficiency (%)
Oral ulcers, n (%) 20 (16) NA 25(OH)D3 2 (3.4) 5 (11.9) 18 (85.7)
None erosive arthritis, n (%) 50 (41) NA deficiency (%)
Serositis, n (%) 12 (10) NA IFN-a level (pg/ml) 45.60  14.62a 59.48  14.51b 85.76  13.80c
Fatigue, n (%) 97 (79) NA (mean  SD)
Renal disorders (proteinuria 51 (41.46) NA IFN-a expression 1.52  0.81a 3.51  2.36b 6.45  1.71c
and/or hematuria) (mean  SD)
Vit-D3 ng/ml (mean  SD) 25.96  8.21 45.82  9.17
Vit-D3 insufficiency (%) 52 (42.3) NA
anti-ds-DNA: anti-double stranded DNA; ESR: erythrocyte sedimen-
Vit-D3 deficiency (%) 25 (20.3) NA
tation rate; IFN: interferon; IQR: interquartile range; NA: not applic-
IFN-a level (pg/ml) (mean  SD) 57.6  20.36 10.63  3.56
able; SD: standard deviation; SLEDAI-2K: systemic lupus
IFN-a expression (mean  SD) 3.06  2.45 1.07  0.31
erythematosus disease activity index; Vit-D3: vitamin D3.
a,b,c
The mean or the median of the same raw data not followed by the
anti-ds-DNA: anti-double stranded DNA; ESR: erythrocyte sedimen- same letters differ significantly, (p < 0.05).
tation rate; IFN: interferon; IQR: interquartile range; NA: not
applicable; SD: standard deviation; SLEDAI-2K: systemic lupus ery-
thematosus disease activity index; Vit-D3: vitamin D3. Furthermore, the serum levels of IFN-a were sig-
nificantly higher in the highly active group of
patients in comparison with the mild and moderate
were not significantly different between different
groups (85.76  13.80 versus 45.60  14.62 and
groups. The SLEDAI-2K score was significantly 59.48  14.51 respectively) as shown in Table 2.
higher in the highly active group as compared
with other groups. Regarding the serum levels of IFN- gene expression
the anti-ds-DNA, ESR, serum creatinine and urea,
they were significantly elevated in highly active There was overexpression of the IFN-a gene in the
group as compared with mild and moderately SLE group compared with the control group
active groups. The high activity group had a signifi- (3.06  2.45 versus 1.07  0.31 respectively) as
cant decrease in serum levels of C3 and C4 com- shown in Table 1. When stratified by SLE disease
pared with other SLE groups. The prevalence (%) activity, the expression level was much higher in the
of 25(OH)D3 deficiency was higher among patients highly active group than in the mild and moder-
of the active group than in the mild and moderate ately active groups (6.45  1.71 versus 1.52  0.81
groups (85.7% versus 3.4% and 11.9%, respect- and 3.51  2.36 respectively) as shown in Table 2.
ively). Moreover, the prevalence of 25(OH)D3 When comparing those with and without lupus
insufficiency was 46.6%, 50% and 14.3% in mild, nephritis, IFN-a gene expression was much higher
moderate and high active SLE groups respectively. in the nephritis group in comparison with those
The serum levels of 25(OH)D3 were significantly without nephritis (5.42  2.02 versus 1.93  0.85
decreased in highly active group when compared respectively).
with mild and moderate groups (Table 2).
Regarding IFN-a serum level, it was significantly Correlation between 25(OH)D3 and SLE
higher in all SLE patients in comparison with disease activity
the healthy control group (57.6  20.36 versus There was a highly significant negative correlation
10.63  11.56 respectively) as shown in Table 1. between serum 25(OH)D3 concentration and
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 IFN-a gene expression in SLE patients
SM Abdel Galil et al.
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Figure 1 (a) The correlation between serum IFN-a level and SLEDAI-2K in all patient group; (b) The correlation between serum
IFN-a level and SLEDAI-2K without nephritis group; (c) The correlation between serum IFN-a level and SLEDAI-2K with
nephritis group.
INF: interferon; SLEDAI: systemic lupus erythematosus disease activity index.

SLEDAI-2K scores in all SLE patients (r ¼ 0.591, (r ¼ 0.640, p < 0.001) in all SLE patients
p < 0.001). This negative correlation was significant in (Figure 1(a)). Moreover, this positive correlation
the moderately active group (r ¼ 0.373, p ¼ 0.014) with SLEDAI-2K score was more significant in
while highly significant in the highly active group the nephritis group than in patients without
of patients (r ¼ 0.616, p < 0.001). Furthermore, nephritis (r ¼ 0.846, p < 0.001 versus r ¼ 0.255,
low serum 25(OH)D3 levels were highly signifi- p < 0.032) (Figure 1(b–c)).
cantly inversely correlated with SLEDAI-2K score
in the nephritis group (r ¼ 0.825, p < 0.001) than
in the group without nephritis. Correlation of IFN- gene expression with
SLE disease activity
Correlation of serum IFN- with SLE
As shown in Figure 2(a–c), a strong positive
disease activity
correlation was observed between IFN-a gene
Serum IFN-a levels showed a highly significant expression and SLEDAI-2K scores (r ¼ 0.748,
positive correlation with SLEDAI-2K scores p < 0.001) in all SLE patients, with a higher
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Figure 2 (a) The correlation between IFN-a expression and SLEDAI-2K in all patient group; (b) The correlation between IFN-a
expression and SLEDAI-2K without nephritis group; (c) The correlation between IFN-a expression and SLEDAI-2K with neph-
ritis group.
INF: interferon; SLEDAI: systemic lupus erythematosus disease activity index

significance in patients with nephritis (r ¼ 0.729, nephritis than in that without nephritis (data not
p < 0.001) than in patients without nephritis shown).
(r ¼ 0.257, p < 0.030).
Correlation between IFN- serum level and gene
Comparison between groups of patients with and expression with serum vitamin D3
without nephritis
There is a significant negative correlation between
The ages of patients and disease durations, were vitamin D3 and IFN-a serum level (Figure 3(a)),
nonsignificantly different between both groups. (r ¼ 0.53, p < 0.001) and gene expression
C3, C4 and 25(OH)D3 were significantly decreased, (Figure 4(a)), (r ¼ 0.454, p < 0.001) in all of our
while other parameters (SLEDAI-2K score, serum study patients. Also, vitamin D3 was significantly
creatinine, urea, 24-hour urine protein, ESR, anti- negatively correlated with both of them, more in
ds-DNA, IFN-a serum level and gene expression) the nephritis group than that without nephritis
were more significantly elevated in the group with Figure 3(b–c) and Figure 4(b–c).
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 IFN-a gene expression in SLE patients
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Figure 3 (a) The correlation between serum IFN-a level and vitamin D3 in all patient group; (b) The correlation between serum
IFN-a level and vitamin D3 without nephritis group; (c) The correlation between serum IFN-a level and vitamin D3 with nephritis
group.
INF: interferon.

Correlation of vitamin D with laboratory parameters of T-helper cells and B-cells, suggests that this vita-
min can play a role in autoantibody production and
In the nephritis group, low 25(OH)D3 levels
in the clinical manifestations of SLE.24,33 Low
showed significant negative correlation with anti-
levels of vitamin D among SLE patients were
ds-DNA (r ¼ 0.537, p < 0.001) and ESR
demonstrated, first, in 1979.34 Since then; several
(r ¼ 0.649, p < 0,001), while positively correlated
studies have confirmed that the majority of SLE
with C3 (r ¼ 0.506, p < 0.001) and C4 (r ¼ 0.691,
patients have decreased levels of vitamin D.35–37
p < 0.001), confirming its potential association It was mentioned that, vitamin D deficiency is
with active lupus nephritis in SLE patients. highly prevalent among SLE patients and severe
deficiency can increases the risk for moderate to
severe disease activity.38
Discussion Our results here, confirm these studies, where, we
have found that vitamin D insufficiency is prevalent
Association of vitamin D levels with immuno- in about 42.3%, while complete deficiency was
logical abnormalities and changes in the expression prevalent in about 20.3% of the total SLE patients,
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Figure 4 (a) The correlation between IFN-a expression and vitamin D3 serum level in all patient groups; (b) The correlation
between IFN-a expression and vitamin D3 serum level without nephritis group; (c) The correlation between IFN-a expression and
vitamin D3 serum level with nephritis group.
INF: interferon

which is concordant with the preceding accumulat- In the present study, we observed that the renal
ing data denoting prevalence of vitamin D insuffi- disorders (proteinuria and/or hematuria), high
ciency and deficiency in SLE patients, of about 38– titers of anti-ds-DNA levels and lower C3, C4
96% and 8–30%, respectively.38 levels as well as high ESR measures were associated
Also, in agreement with several previous stu- with a significant decrease in the mean values of
dies,6,22,38–42 our results demonstrated low levels serum 25(OH)D3 concentrations, confirming its
of 25(OH)D3 to be associated with higher SLE dis- close relation to active lupus nephritis and higher
ease activity measured by SLEDAI-2K score, while disease activity,45–49 and in favor with the earlier
we are contradictory to other studies which found observations reporting associated low levels of
no association.43,44 The wide variation between dif- 1,25(OH)2D and 25(OH)D with chronic kidney
ferent studies can be related to different ethnicities diseases.50 On the contrary, Monticielo et al.35 did
of participants in each study, geographic location, not find any significant correlation between vitamin
and/or seasonal variations at the time of these D deficiency and clinical or laboratory manifest-
studies. ations of SLE. Also, El Garf et al.13 mentioned
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 IFN-a gene expression in SLE patients
SM Abdel Galil et al.
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that, there was no significant correlation between This leads to local synthesis of IFN-a by primary
levels of 25(OH)D3 and disease activity index, dis- human renal proximal tubular cells (RPTECs). By
ease manifestations (nephritis or neuropsychiatric this autocrine loop, IFN-a might have a pathogenic
manifestations) or laboratory parameters (ESR, role in lupus nephritis activating pro-inflammatory
anti-ds-DNA, low complement levels) that may and antigen presentation pathways in RPTECs.63
reflect the disease activity or severity in a cohort The observed significant inverse relationship
of children with juvenile-onset SLE. This discrep- between vitamin D level and IFN-a gene expression
ancy may also due to the shorter disease duration in and serum level in our study, suggests an indirect
children with SLE than with the adults. role of vitamin D in the pathogenesis of lupus
Several possible explanations for the vitamin D nephritis through its effect on IFN-a secretion
deficiency among lupus patients have been men- and gene expression by the activated DCs.22,23,39
tioned before.14–18,51–53 Additionally, urinary
losses of 25(OH)D3 and D-binding protein in pro-
teinuric nephropathies, as occurred in lupus neph- Conclusion
ritis, contribute to vitamin D deficiency.54 All of
these factors help in introducing SLE patients in a
vicious circle of deteriorating renal function and In conclusion, low levels of serum 25(OH)D3 are
descending serum level of vitamin D. commonly prevalent in SLE patients and have an
Significant elevation of IFN-a gene expression, inverse relationship with SLE disease activity and
as well as its serum levels, in SLE patients than in active lupus nephritis, through its effects on IFN-a
their matched healthy control (HC) group. In add- gene expression and secretion in plasma by mono-
ition to their negative correlation with serum cytes and dendritic cells. The positive correlations
25(OH)D3 and more significant elevation in the between IFN-a gene expression and serum levels
group with than that without nephritis, was with SLE disease activity, raise the possibility of
observed in our study. These results are in line using this cytokine as a biomarker of the disease,
with previous studies which found that patients especially for lupus nephritis, that needs more
with lupus have higher serum IFN-a activity as extended follow up and observational studies.
compared with healthy unrelated individuals.55 Vitamin D supplementations should be added as
We are also in agreement with another study per- an important supportive immunomodulatory treat-
formed on Indian SLE patients, that showed a sig- ment besides cytotoxic, immunosuppressive and
nificant negative correlation between 25(OH)D3 other lines of treatment of SLE.
levels and plasma IFN-a levels and gene expression,
in addition to the significant negative correlation
between both of them and disease activity.39 Declaration of conflicting interests
It was proved that vitamin D acts upon inhib-
ition of dendritic cell maturation, decreasing the The authors declared no potential conflicts of inter-
expression of IFN-a induced genes in SLE est with respect to the research, authorship, and/or
patients56 and can inhibit monocyte production of publication of this article.
inflammatory cytokines such as IL-1, IL-6, IL-8,
IL-12 and tumor necrosis factor (TNF)-a.57
Also, we have found IFN-a serum level signifi- Funding
cantly elevated in patients of the nephritis group.
This is consistent with previous results reporting The authors received no financial support for the
higher serum IFN-a significantly prevalent in SLE research, authorship, and/or publication of this
patients complaining from cutaneous and renal dis- article.
ease,58–60 and thus positively correlating with SLE
disease activity.19 On the other hand, it was proved
that IFN-a gene overexpression occurs in lupus References
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Clin Exp Rheumatol 2005; 23(Suppl.39): S120–S132.
infiltrating plasmacytoid DC and renal tubular 3 Teresa K, Chen-Derek M. Fine top 10 developments in lupus neph-
epithelial cells in patients with lupus nephritis. ritis. Curr Rheumatol Rep 2013; 15: 358.

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