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1- بررسی تغییرات اولیگوکلونال باند (OCB )در مایع مغزی نخاعی بیماران مبتلابه ام اس(MS )مغزی یا مولتیپل اسکلروز در مراجعه کنندگان به بیمارستان لقمان تهران در طی  سالهای 1370 الی1376 به استاد راهنمایی جناب دکتر کوروش قره گوز لی رئیس انجمن ام اس ایران.

 

تحقیق1

قلم

 

 

 

 

 

 

 

2- بررسی موارد آنتی فسفو لیپید آنتی بادی در بیماران مبتلا به لوپوس اریتماتوس مراجعه کننده به بیمارستان اکباتان همدان در طی سالهای 1386و1387 و ارتباط آن با علائم آنتی فسفو لیپید سندرم.به استاد راهنمایی سرکار خانم دکترزهرا بصیری روماتولوژیست. 

این مقاله در مجله ی JOURNALS  TUMS سال 2013 به چاپ رسیده است.

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The Prevalence of Anticardiolipin Antibody in Patients
with Systemic Lupus Erythematosus and Its
Association with Clinical Manifestations

Zahra Basiri1, Mahmoud Gholyaf1, Mansureh Faridnia1, Ebrahim Nadi2, and Mandana Bairanvand2

1 Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2 Department of Internal Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Received: 26 Dec. 2011; Received in revised form: 2 Jan. 2013; Accepted: 4 Jan. 2013

Abstract-The central immunological disturbance in systemic lupus erythematosus (SLE) is autoantibody
production. Some of these antibodies affecting components of the cell nucleus are the major characteristics of
SLE. The present study was aimed to assess importance of anticardiolipin (ACL) antibody and its association
with clinical state in SLE patients. A cross sectional study was performed on 100 patients with SLE referred
to rheumatology outpatient clinic in Ekbatan hospital in Hamadan (Iran) between 2007 and 2008. Serum
samples were extracted and screened for IgG and IgM using an ACL enzyme-linked immunosorbent assay.
Up to 36% of patients were positive for ACL antibody that was more frequent in women than men (39.8%
versus 8.3%). No association was revealed between ACL antibody and age. Clinical manifestations of
antiphospholipid antibody syndrome were observed in 23.0% of patients that was more prevalent in ACL
positive group compared with ACL negative group (41.7% versus 125%). The prevalence of other
manifestations including pregnancy-related disorders (recurrent abortion), central nervous system defects, and
deep vein thrombosis was 33.3%, 25.0%, and 30.6% in ACL positive group and was 9.4%, 7.8%, and 7.8% in
ACL negative group that all were more frequent in the former group. The prevalence of thrombocytopenia
was also higher in ACL positive group than another group (22.2% versus 15.6%). Among ACL positive
patients with clinical manifestations of antiphospholipid antibody syndrome, 86.6% had medium to high titer
of ACL. Our study emphasized value of (ACL) antibody to assess clinical status in SLE patients.
© 2013 Tehran University of Medical Sciences. All rights reserved.
Acta Medica Iranica, 2013; 51(1): 35-40.

Keywords: Anticardiolipin antibody; Antiphospholipid syndrome; Systemic lupus erythematosusآدمک و کتاب

Introduction

Systemic lupus erythematosus (SLE) is a multisystem
autoimmune disease which is associated with formation
of a variety of autoantibodies. Antiphospholipid
antibody (APL) is an autoantibody that is linked to comorbidities
such as recurrent arterial and venous
thrombosis. The increased level of APL occurs primarily
or secondary to SLE or other autoimmune disorders
(1,2). In the presence of this antibody, the risk of
clotting can be significantly increased that its elevated
level is shown to be associated with thrombotic
symptoms of antiphospholipid syndrome (APS) and
SLE (3). In a prospective study on 500 patients with
SLE, recurrent venous thrombosis, thrombocytopenia,
hemolytic anemia, recurrent fetal loss, and leg ulcers

were strongly associated with the level of anticardiolipin
antibody (ACL) (4).

According to the Sapporo criteria, APS can
potentially be detected in subjects with clinical criteria
of arterial, venous or small-vessel thrombosis as well as
in those with pregnancy-related morbidities including
recurrent fetal loss before the 10th week of gestation,
unexplained fetal death at or beyond the 10th week of
gestation, or premature birth due to placental
insufficiency, eclampsia or preeclampsia (5,6).

The immunoglobulin isotype of ACL include IgG,
IgM or IgA that can be detected using enzyme-linked
immunosorbent assays (ELISA). The IgG isotype is
most strongly associated with thrombosis (7). ACL
antibodies are reported as a titer specific to the antibody
isotypes (IgG, IgM, or IgA phospholipid antibody titer),

Corresponding Author: Ebrahim Nadi
Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Tel: +98 811 8380704, Fax: +98 811 8226035, E-mail: nadi@umsha.ac.ir

Downloaded from http://journals.tums.ac.ir/ on Friday, February 22, 2013

Anticardiolipin antibody in patients with SLE

but because of the limited accuracy and reliability of
assays, consensus guidelines recommend semi-
quantitative reporting of results as low, medium, or high
titer (8).

APL has been also shown to bind some antigens
such as prothrombin, annexin V, and .2-glycoprotein I
(.2GPI). Antibodies reacting with these antigens may be
directly involved in the pathogenesis of APL-associated
symptoms (9,10). Exact mechanism of coagulopathies in
presence of these autoantibodies is still unknown. Not
only APL can directly bind to platelet surfaces and
promote thrombo-agglutination in vitro (11), but it can
also affect the vascular endothelium and cause
prothrombotic events (12,13).

In Chinese patients with SLE, both IgG and IgM
isotypes of ACL and anti-.2GPI have been detected with
ELISA kit. In a study on those patients, the highest
predictive accuracy of thrombosis was with the presence
of a low or higher titer of either ACL (>12 RU/ml) or
anti-.2GPI (>20 RU/ml). Also, in patients with SLE
especially in those with other risk factors for thrombosis
and those who treated with glucocorticoids, a transient
low or high titer of ACL or anti- .2GPI antibody had a
good predictive value for the diagnosis of thrombosis
(14,15). In these thrombotic events, long-term
anticoagulation therapy is a choice protocol. The
patients suffering from SLE and APS should be
managed with long term anticoagulation, and a target
international normalized ratio (INR) of 3 is
recommended for their follow-up. New clotting event in
patients treated to this target of INR can be decreased
compared to patients treated with lower INR (15).

In the present study, we first evaluated the
prevalence of positive ACL antibody in SLE patients
and then assessed its association with clinical
manifestations of SLE.

Materials and Methods

One hundred SLE patients (88 women and 12 men)
referred to rheumatology outpatient clinic at Ekbatan
hospital in Hamadan city were recruited for this cross-
sectional study. All patients fulfilled the 1997 revised
American College of Rheumatolog (ACR) criteria for
SLE. All participants were subjected to full history,
complete clinical examination, routine laboratory
investigations, and IgG and IgM ACL test.
Blood samples were taken at the time of patients’
attendance.

ELISA were used to assess ACL level that scored as

negative (<10 units) or positive (>10 units) for final
analysis. ACL IgG was also classified as high (>80
unit/ml), medium (20-80 unit/ml), and low (10-20
unit/ml). Sensitivity and specificity of the test was
estimated as 91.7% and 97.6%, respectively. Written
informed consent was obtained from all. The data
containing clinical manifestation of APS and APL
antibody levels were collected in study checklist and
were analyzed statistically by using SPSS software
(version 15.0) along with Chi-square test or Fisher’s
exact test.

Results

The mean age of participants was 42 years (ranged 1150
years) and 88% were female. Up to 36% of patients
with SLE were positive for ACL antibody (39.8% of
women and 8.3% of men, P<0.05). In the subgroups of
patients with positive and negative ACL, no difference
was found in term of mean age (P=0.860). Clinical
manifestations of APS were detected in 23.0% of total
patients that was significantly more prevalent in those
with positive ACL antibody compared to negative ACL
antibody group (41.7% versus 12.5%, P<0.05) (Table
1). Besides, clinical manifestations of APS were not
seen in 87.5% of SLE patients with negative ACL test.
In SLE patients with manifestations of APS, ACL test
was positive in 65.0% and was negative in 35.0%.
While, in SLE patients without clinical manifestations of
APS, ACL test was negative in 72.7%. In 29.0% of
patients with SLE, APS manifestations and results of
ACL test were inconsistent. There were significant
differences in overall prevalence of pregnancy-related
complications such as recurrent abortion, central
nervous system disorders and deep vein thrombosis in
SLE patients with and without positive ACL test (Table
2). The prevalence of other manifestations including
pregnancy-related disorders (recurrent abortion), central
nervous system defects, and deep vein thrombosis
was 33.3%, 25.0%, and 30.6% in ACL positive
group and was 9.4%, 7.8%, and 7.8% in ACL
negative group that all were more frequent in the
former group. The prevalence of thrombocytopenia
was similar in ACL positive group than another
group (22.2% versus 15.6%). The prevalence of
cardiovascular disorders, skin lesions, and arterial
thrombosis in SLE patients with positive ACL test was
8.3%, 5.6%, and 5.6% and in SLE patients with negative
ACL test was 6.3%, 0.0%, and 1.6% with no significant
discrepancy.

36 Acta Medica Iranica, Vol. 51, No. 1 (2013)

Z. Basiri, et al.
Table 1. Clinical manifestations of APS in SLE patients with positive and negative ACL test.
ACL test With clinical manifestation
of APS
With clinical manifestation
of APS
Positive 15 (41.7) 21 (58.3)
Negative 8 (12.5) 56 (87.5)
Total 23 (23) 77 (77)
Data are presented as number (%)
P-value
0.001

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Table 2. Different types of clinical manifestations of APS in SLE patients with positive and negative ACL test.
ACL test Pregnancy Venous CNS Cardiac Skin Arterial
disorders thrombosis disorders disorders disorders thrombosis

Test (+) 12 (33.3) 11 (30.6) 9 (25.0) 3 (8.3) 2 (5.6) 2 (5.6)
Test (-) 6 (9.4) 5 (7.8) 5 (7.8) 4 (6.3) 0 (0.0) 1 (1.6)
P-value 0.003 0.003 0.017 0.690 0.120 0.290

Data are presented as number (%)

In patients with SLE and positive ACL, the titer level
of ACL was low in 50.0%, medium in 19.4%, and high
in 30.6%. There was a significant difference in ACL
titer level between the groups with positive and negative
APS test. In SLE patients with clinical manifestations of
APS and positive for ACL, IgG ACL was scored as
medium to high titer in 86.6% compared with 23.8% in
SLE patients with ACL positive test, but without clinical
manifestations of APS.

Discussion

Our study shows that the incidence of clinical
manifestations of APS and its related complications such
as pregnancy-related disorders (recurrent abortion),
central nervous system defects, and deep vein
thrombosis in SLE patients with negative ACL test was
significantly lower than those with positive ACL test.
The previous studies similarly showed that the risk of
thrombotic events was increased in positive APL test
and has concluded that this autoantibody has an
important role in the pathogenesis of APS (16,17). Up to
5% to 70% of SLE patients produce some types of ACL
(18,19). In an analysis on 29 published series including
more than 1000 patients with SLE, the average range of
for the lupus anticoagulant was 34% and for ACL was
44%. The significant association was also found
between the presence of either antibody and a history of
thrombosis, neurological disorders, or thrombocytopenia
(20). In another study, 37 patients with SLE were
screened for APLAS (ACL antibody, lupus
anticoagulant, or both) during a 27 months follow-up. In

that study, 27% had evidences of APLAS and 24% had
positive antibody but were asymptomatic. Therefore
routine screening for ACL antibody for all patients
with SLE is stron Acta Medica Iranica, Vol. 51, No. 1 (2013)