ORIGINAL ARTICLE
Annexin A5 and anti-annexin antibodies in patientswith systemic lupus erythematosus
Antoni Hrycek • Paweł Cieslik
Received: 16 June 2010 / Accepted: 16 January 2011 / Published online: 5 February 2011
� Springer-Verlag 2011
Abstract Plasma levels of annexin A5 (ANX A5) and
anti-annexin A5 (aANX A5) antibodies were evaluated in
51 women with systemic lupus erythematosus (SLE). The
results were compared between the total SLE group, sub-
groups on/without immunosuppressive therapy and the
control (28 women). The relationships between ANX
A5/aANX A5 antibodies levels and laboratory vari-
ables (anti-cardiolipin antibodies—aCL, total cholesterol,
thrombocyte count, activated partial thromboplastin time—
APTT, prothrombin time, international normalized ratio–
INR) were performed in the total SLE group and in the
patient subgroups identified as the arithmetic mean of ANX
A5 concentration in the control plus 1–4 standard devia-
tions (SD). The whole SLE group and the subgroup on
immunosuppression showed significantly higher ANX A5
and IgG aANX A5 antibodies concentrations. A weak
positive correlation was found between ANX A5 and
thrombocyte count, a moderate one between IgG and IgM
aANX A5 antibodies, a weak negative correlation between
IgG aANX A5 and APTT in the whole SLE group. SLE
subgroups with ANX A5 concentrations higher than the
control mean plus 3 or 4 SD showed a weak/moderate
negative correlation of this parameter with aANX A5
antibodies, moderate one with IgG aCL antibodies levels, a
moderate positive correlation with cholesterol concentra-
tion, moderate/high positive correlations with thrombocyte
count. The association between plasma ANX A5/IgG
aANX A5 levels and severity of disease was noticed. The
role of aANX A5 and IgG aCL antibodies as causative
factors of increased ANX A5 levels was suggested, and the
relationship between ANX A5 and thrombocyte count was
revealed.
Keywords SLE � Annexin A5 � Antibodies �Associations � Therapy
Introduction
Due to structural similarities, twelve of over a thousand
proteins of the annexin superfamily have been classified in
the annexin A family [1–4]. Under physiological condi-
tions, annexins are involved in cell signaling, membrane
trafficking events, the process of blood coagulation, and
inflammation [1, 2, 5–8]. The best known is annexin A5
(ANX A5—previously also referred to as placental anti-
coagulant protein I, vascular anticoagulant a, calphobindin
I) [3]. It has been found intracellularly in cellular vesicles
and plasma membranes. It has been identified in the
endothelium, chondrocytes, osteoblasts, Schwann cells,
hepatocytes, apical surface of placental syncytiotropho-
blasts, and in heart tissues, optical nerve and bronchi
[1, 7, 9]. Although it is an intracellular protein, its small
amounts are also detected in the plasma, cerebrospinal
fluid, urine from healthy persons [4], amniotic fluid, and
semen plasma [1].
ANX A5 is a natural anticoagulant with a high calcium-
dependent binding affinity for negatively charged phos-
pholipids [10, 11]. It also modulates the activity of
phospholipase A2 and protein kinase C (PKC) both in vitro
and in vivo [7, 8, 12–14]. Through inhibiting prothrombin
activation, ANX A5 prevents arterial and venous thrombus
A. Hrycek � P. Cieslik
Department of Internal, Autoimmune, and Metabolic Diseases,
Medical University of Silesia, ul. Medykow 14,
40-752 Katowice, Poland
A. Hrycek (&)
ul. Tysiaclecia 86a/34, 40-871 Katowice, Poland
e-mail: [email protected]
123
Rheumatol Int (2012) 32:1335–1342
DOI 10.1007/s00296-011-1793-2
formation [1, 7]. The anti-thrombotic effect of ANX A5 is
mediated by its preferential binding to phosphatidylserine
expressed on the surface during the destruction of the cells
[15]. Phosphatidylserine exposure is the physiological
signal for the processes of coagulation and apoptosis.
Extracellular ANX A5 accumulation helps recognize the
signaling and binds with phosphatidylserine preventing the
coagulation process [1, 7, 11]. Similar to prothrombin,
ANX A5 is phospholipids cofactor, and it is assumed that it
forms phospholipid–protein complex, which is the target
for anti-phospholipid antibodies action [10, 16].
IgG and IgM anti-annexin A5 antibodies (aANX A5
antibodies) constitute another problem; they are among
anti-phospholipid/anti-cofactor antibodies that reduce the
availability of ANX A5. The two most important clinical
types of anti-phospholipid antibodies are anti-cardiolipin
(aCL) antibodies and lupus anticoagulant (LA), frequently
detected in patients with systemic lupus erythematosus
(SLE). Common clinical presentations of patients with aCL
antibodies are venous or arterial thrombosis, thrombocy-
topenia, and pregnancy complications such as intrauterine
fetal demise, etc. It should be emphasized that the signifi-
cance of aANX A5 antibodies as well as ANX A5 in SLE
patients has not been clearly defined [10]. However, it has
been suggested that these antibodies might mediate some
reduction in ANX A5 anticoagulant properties [11].
SLE is an autoimmune disease with disturbances in the
process of clearance of apoptotic cells [8, 17] and the
dominant role of extracellular DNA in pathogenesis of
disease [15]. Apoptotic cells display characteristic mor-
phological and surface changes related to a key functional
phenomenon, which is the above-mentioned phosphati-
dylserine expression [15].
The purpose of the present study was to assess plasma
ANX A5 and aANX A5 antibodies levels and their associ-
ations with the severity of the disease in treated SLE
patients. A further aim of this study was to determine rela-
tionships between plasma concentrations of ANX A5/aANX
A5 antibodies and selected laboratory parameters in the
examined SLE group. It was expected that the obtained
results might allow to find some cause-effect phenomena
between the analyzed parameters, and consequently it might
be advantageous in the management of SLE.
Materials and methods
Patients and controls
In this retrospective study, the investigations were carried
out in 51 women with SLE (mean age 52 ± 16 years)
admitted to the hospital for the routine control who had
already received treatment (of several-month to several-
year duration). The following drugs were applied as single
or in various combinations—prednisone (7.5–15 mg per
day in 39 patients), immunosuppressive drugs—azathio-
prine (50–100 mg per day in 11 patients), cyclophospha-
mide (in cyclic courses 200 mg per day in 1 patient),
cyclosporine A (50–100 mg per day in 2 patients) and
prolactin-suppressive drug, dopamine agonist—quinago-
lide (Norprolac 25–50 lg per day in 5 patients). When
necessary, patients were allowed to take nonsteroidal
anti-inflammatory drugs (8 patients) and analgesics.
In 41 patients, immunosuppressive therapy was applied, 10
patients were without immunosuppression, and they
received Norprolac or nonsteroidal anti-inflammatory
drugs. All study subjects met at least four of the 1982
American Rheumatism Association (ARA) criteria for the
diagnosis of SLE [18], updated in 1997 [19]; most were
considered to have mild-to-moderate disease. The control
group consisted of 28 healthy medication-free women
(mean age 50 ± 17 years i.e. age distribution similar to the
patient group) recruited from members of the staff of
medical department. The patients and control subjects were
questioned in relation to tobacco smoking, contraception or
hormone-replacement therapy, history of thrombosis, and
also pre- or post-menopausal period was determined. In the
patient group, 9 women (18%) and 5 in the controls (18%)
were current smokers, 4 patients (8%) and 3 control sub-
jects (10%) applied oral contraceptive pills or hormone-
replacement therapy, the history of thrombosis was
revealed only in the patient group (5 women), 34 patients
were pre-menopausal, 17 patients post-menopausal and 18
controls/10 controls, respectively.
On the day of blood sampling, clinical evaluation was
performed including examination and calculation of the
SLE disease activity index (SLEDAI) score. Our patients
demonstrated the involvement of three to four of the nine
possible organ systems; all treated subjects had a SLEDAI
score of \10 during this examination. Arithmetic mean
(X) and ± standard deviation (SD) of SLEDAI score in the
subgroup of 41 patients with immunosuppressive therapy
and in 10 patients without immunosuppression were the
following: 7.0 ± 1.52 and 5.80 ± 1.23, respectively,
P \ 0.05. None of the patients presented with severe renal
or hepatic dysfunction.
The serological features were assessed in each patient.
The laboratory indicators of seroactivity in SLE and the
screening for autoimmune disease included erythrocyte
sedimentation rate, anti-DNA antibodies, antinuclear anti-
bodies, aCL antibodies, and complement factor C3 levels
in the serum. These tests were performed using standard
techniques.
All blood samples were collected mid-morning between
7 and 8 am from fasting and resting patients and were
stored at the temperature of below -70�C before use.
1336 Rheumatol Int (2012) 32:1335–1342
123
The plasma samples were randomly coded, and the mea-
surements were performed blind. The study was approved
by the local independent bioethics committee; all patients
gave their written consent.
Laboratory measurements and investigation scheme
Clinical measurements included plasma ANX A5, and IgG
and IgM aANX antibodies levels. The tests were performed
by commercially available enzyme-linked immunoassay
(ELISA) using IMUCLONER kits in a lQuant spectro-
photometer ELISA. The following investigation scheme
was adopted: (1) the comparison of the results (a) between
SLE group (51 treated female patients) and healthy con-
trols (28 women), (b) between separated SLE subgroup
receiving immunosuppressive therapy (41 patients) and
healthy controls, (c) between SLE subgroup without
immunosuppressive therapy (10 women) and the control,
(d) between SLE subgroup receiving immunosuppressive
therapy (41 patients) and SLE subgroup without immuno-
suppression (10 women), (2) the evaluation of the rela-
tionships in the whole SLE group (a) between the
concentrations of ANX A5/aANX A5 antibodies and the
following laboratory variables determined by standard
techniques (aCL antibodies, total cholesterol concentration
in serum, platelet number, activated partial thromboplastin
time—APTT, prothrombin time, international normalized
ratio-INR), (b) between ANX A5 and IgG/IgM aANX A5
antibodies levels, (c) between IgG aANX A5 and IgM
aANX A5 antibodies, (3) the determination of the rela-
tionships between ANX A5 concentrations and the
above-mentioned laboratory variables in SLE subgroups
identified on the basis of the arithmetic mean of ANX A5
concentration in the control group plus 1–4 standard
deviations (SD).
Statistical analyses
The obtained results were analyzed statistically by calcu-
lating X and ±SD and also median values were established
and minimum and maximum ranges were included. The
results were subject to normal distribution analysis by the
Shapiro–Wilk’s test. When the distributions of the exam-
ined variables were normal, Student’s t-test for indepen-
dent data was used. When the distributions of the examined
variables were non-normal, nonparametric tests were per-
formed in further calculations. Differences between vari-
ables were analyzed with the U Mann–Whitney’s test.
Correlations between variables were measured with the
Pearson’s correlation coefficient (r). The difference
between arithmetic means was considered statistically
significant at P \ 0.05 and highly statistically significant at
P \ 0.001.
Results
A highly statistically significant difference was found
between mean plasma level of ANX A5 of the total SLE
group (1.34 ± 0.98 ng/ml, median = 0.95, range
0.52–5.51) when compared with the control group
(0.77 ± 0.22 ng/ml, median = 0.76, range 0.48–1.34);
P \ 0.001. This group also demonstrated a statistically
significantly higher plasma concentration of IgG aANX A5
antibodies than the control (2.35 ± 2.25 and 1.53 ± 0.76
AU/ml, respectively; P \ 0.05, median = 1.95, range
0.63–15.13 and median = 1.52, range 0.53–3.95, respec-
tively). No significant difference was seen in the mean
plasma levels of IgM aANX A5 antibodies between the
study group and the control group (2.23 ± 1.22 AU/ml and
2.30 ± 0.95 AU/ml, respectively, median = 2.05, range
0.60–6.27 and median = 1.96, range 1.21–3.90, respec-
tively) (see also Fig. 1).
SLE patients on immunosuppressive therapy had a
highly statistically significant difference in the mean plasma
concentration of ANX A5 compared to the control
(1.43 ± 1.07 ng/ml and 0.77 ± 0.22 ng/ml, respectively;
P \ 0.001, median = 0.95, range 0.57–5.51 for the sub-
group of patients). Their mean plasma level of IgG aANX
A5 antibodies was significantly higher than that of the
control group (2.23 ± 2.20 AU/ml and 1.53 ± 0.76 AU/ml,
respectively; P \ 0.05, median = 1.95, range 0.63–15.13
for the subgroup of patients). The mean values of IgM aANX
A5 antibodies levels did not show statistically significant
difference between the study subgroup and the control group
(2.20 ± 1.26 and 2.30 ± 0.95 AU/ml, respectively, med-
ian = 2.05, range 0.60–6.27 for the patient subgroup). Also,
no statistically significant differences were found between
plasma IgG and IgM aANX A5 antibodies levels in SLE
subgroup without immunosuppressive therapy and the
control (IgG: 2.66 ± 2.55 and 1.53 ± 0.76 AU/ml,
respectively, median = 1.85, range 0.63–9.41 for the sub-
group of patients; IgM: 2.32 ± 1.09 and 2.30 ± 0.95
AU/ml, respectively, median = 2.00, range 1.03–4.06 for
the subgroup of patients). The mean plasma ANX A5 level
was slightly higher in SLE patients without immunosup-
pression than in the healthy controls (0.99 ± 0.36 and
0.77 ± 0.22 ng/ml, respectively, median = 0.93, range
0.52–1.62 for the patient subgroup); the difference was close
to statistical significance (P \ 0.052). The differences of
mean values concerning ANX A5, IgG, and IgM aANX A5
antibodies did not reveal statistical significances when the
results between the above-mentioned subgroups of SLE
patients were compared (1.43 ± 1.07 ng/ml, 2.23 ± 2.20
AU/ml, 2.20 ± 1.26 AU/ml in the subgroup on immuno-
suppressive therapy and 0.99 ± 0.36 ng/ml, 2.66 ± 2.55
AU/ml, 2.32 ± 1.09 AU/ml in SLE subgroup without
immunosuppression, respectively).
Rheumatol Int (2012) 32:1335–1342 1337
123
The analysis of the relationships, performed in the total
SLE group, revealed a moderate positive correlation
between IgG aANX A5 and IgM aANX A5 antibodies
levels, a weak positive correlation between the levels of
ANX A5 and the peripheral blood thrombocyte count, and
a weak negative correlation between IgG aANX A5 anti-
bodies levels and APTT (Table 1). Correlations with other
laboratory variables tested did not reach the level of sta-
tistical significance (Table 1).
Correlations between ANX A5 level and IgG/IgM
aANX A5 antibodies levels and the laboratory variables
results in the subgroups of the SLE patients with ANX A5
cutoff defined as arithmetic mean of the control plus 1–4
SD are presented in Table 2. The subgroups of SLE
patients with three or four SD above the mean of the
control group had weak/moderate negative ANX A5 cor-
relations with IgG and IgM aANX A5 antibodies, respec-
tively, moderate negative correlation with IgG aCL, and
moderate but positive correlation coefficient with serum
cholesterol level. These SLE subgroups also showed
moderate and high positive correlation coefficients
between ANX A5 and thrombocyte count (Fig. 2). No
other relationships were found between ANX A5 concen-
trations of the above-mentioned SLE subgroups, which
were considered together, and the obtained results of other
laboratory variables.
Discussion
As already mentioned, ANX A5 is a protein with potent
anti-thrombotic properties preventing coagulation pro-
cesses. However, its anti-thrombotic potential has not so
far been used in clinical practice. ANX A5 also plays an
important regulatory role in apoptosis [5]. However,
it should be emphasized that the role of circulating ANX
A5 and aANX A5 antibodies remains to be defined.
Our own investigations have revealed significantly
higher plasma concentration of ANX A5 accompanied by
significantly higher IgG aANX A5 antibodies levels in the
total group of SLE patients and SLE patients undergoing
immunosuppressive therapy, compared to the control.
AN
X A
5 pl
asm
a co
ncen
trat
ion
[ng/
mL]
0,0
0,5
1,0
1,5
2,0
2,5
IgM
aA
NX
A5
antib
odie
s pl
asm
a co
ncen
trat
ion
[AU
/mL]
0
1
2
3
4
5
IgG
aA
NX
A5
antib
odie
s pl
asm
a co
ncen
trat
ion
[AU
/mL]
0
1
2
3
4
5
SLEgroup
SLEgroup
SLEgroup
Controlgroup
Controlgroup
Controlgroup
Fig. 1 Plasma levels of ANX A5 and aANX A5 antibodies
(mean ± SD values are shown) in the total SLE group and in the
controls
Table 1 Correlation coefficients (r) between ANX A5 or IgG and IgM aANX A5 antibodies levels and the results of other laboratory variables
investigated in peripheral blood in the total SLE group
Pearson’s (r)
Parameter aANX A5 IgG aANX A5 IgM aCL IgG aCL IgM Cholesterol Thrombocytes APTT PT INR
ANX A5 N = 51 0.0571 -0.0114 -0.1298 0.1102 0.1268 0.2372 -0.0083 -0.0977 -0.0830
aANX A5 IgG N = 51 _ 0.3265 0.1447 0.0624 -0.1382 -0.0170 20.2214 -0.0875 -0.0875
aANX A5 IgM N = 51 _ _ -0.0935 0.0332 -0.0002 -0.0374 -0.0003 -0.0189 -0.0033
Statistically significant results are in the bold
1338 Rheumatol Int (2012) 32:1335–1342
123
Patients with mild SLE severity treated with dopamine
receptor agonists or nonsteroidal anti-inflammatory drugs
(only those individuals can receive such therapies [20]) did
not show significant differences in plasma IgG and IgM
aANX A5 antibodies levels compared to the control.
Plasma concentration of ANX A5 in the patients treated
with dopamine receptor agonist or nonsteroidal anti-
inflammatory drugs was higher than in the control group
with the difference which was only close to, but did not
reach the level of statistical significance.
It has been well established that plasma ANX A5 ele-
vation in women with recurrent miscarriages might result
from its replacement by anti-phospholipid antibodies; thus,
excess annexin might originate from ANX A5 pool highly
expressed by placental trophoblasts [2, 9, 12]. In the
pathomechanism of thrombus formation, the possibility of
ANX A5 displacement from endothelial surface should be
considered. Animal experiments have shown that, similar
to sensu lato anti-phospholipid antibodies, specific aANX
A5 antibodies are capable of replacing and reducing ANX
A5 activity on cell surfaces [12]. However, it has been
suspected that, opposite to anti-phospholipid antibodies,
specific aANX A5 antibodies might also simultaneously
interfere with ANX A5 function. Their actual role requires
further studies [7] because there has been conflicting evi-
dence [21].
Irrespective of the pathomechanism of ANX A5 and IgG
aANX A5 antibodies actions in SLE, it is worth consid-
ering the mechanisms that could possibly lead to excess
amounts thereof in the plasma of SLE in our study subjects.
Taking into consideration highly statistically significant
increase in ANX A5 concentration in the total group and in
SLE subgroup on immunosuppressive therapy and also
noticeable higher mean level of this protein in the subgroup
without immunosuppression the essential role of ANX A5
may be suggested. ANX A5 as an antigen might stimulate
the production of specific aANX A5 antibodies [7] with a
consequent increase in these antibodies concentrations in
plasma. However, we did not observe any significant
associations between elevated plasma level of ANX A5 and
IgG and IgM aANX A5 antibodies as well as IgG and IgM
aCL levels in the whole SLE group. This is, to some extent,
in accordance with the results of other authors, who did not
find any causative relationship between anti-phospholipid
antibody concentrations and plasma ANX A5 in SLE
patients [12]. An analysis of these relationships in our SLE
subgroups with an ANX A5 cutoff defined as the arithmetic
mean of the control plus 1–4 SD revealed a negative cor-
relation (weak or moderate) between plasma ANX A5 and
IgG/IgM aANX A5 and IgG aCL antibodies concentration
in those SLE patients whose ANX A5 levels were higher
than the control mean plus 3 or 4 SD. Therefore, we think
that the obtained result may indicate the main role of the
antibodies in the pathomechanism of the observed phe-
nomena i.e. the highest statistical difference in relation to
ANX A5 between SLE patients (the total group and the
subgroup on immunosuppressive therapy) and the control,
concomitant higher level of IgG aANX A5 antibodies in
these SLE patients, negative correlation of ANX A5 with
IgG/IgM aANX A5 and IgG aCL antibodies in the separated
subgroups. Thus, it might be suggested that in treated SLE
patients, an increase in production and in binding of these
antibodies in organ cells is associated with a consequent
ANX A5 release from the cell surface. This could account
for the phenomena observed in our investigations.
It has also been found that ischemia might cause ANX
A5 concentrations increase [3]. However, attempts to
determine ANX A5 levels in plasma of patients with ath-
erosclerotic disease did not give convincing results; lower
plasma concentrations were found in the acute stage of
myocardial infarction [22]. Taking into account the role of
cholesterol in atherosclerotic events, its serum level was
determined in our patients. Although the total SLE group
did not show correlations between plasma level of ANX
Table 2 Correlation coefficients (r) between concentrations of ANX A5 expressed as[arithmetic mean plus SD (1–4 SD) for the control and
other laboratory variables results obtained in SLE subgroups
Pearson’s (r)
Parameter aANX A5
IgG
aANX A5
IgM
IgG aCL IgM
aCL
Cholesterol Thrombocytes APTT PT INR
ANX A5; above the control
mean ? 1SD, N = 24
-0.0728 -0.22O1 -0.1266 0.0635 0.0807 0.3268 -0.1049 -0.1426 -0.1543
ANX A5; above the control
mean ? 2SD, N = 19
-0.1967 -0.1306 -0.2980 -0.0321 0.1863 0.3901 -0.0067 -0.1666 -0.1852
ANX A5; above the control
mean ? 3SD, N = 16
20.2922 20.2131 20.4180 -0.0945 0.3936 0.4223 0.0481 -0.1209 -0.2159
ANX A5; above the control
mean ? 4SD, N = 11
20.3649 20.3531 20.5049 -0.2120 0.3720 0.7670 0.2219 -0.0815 -0.1374
Statistically significant results are in the bold
Rheumatol Int (2012) 32:1335–1342 1339
123
A5 and cholesterol concentration, SLE subgroups with an
ANX A5 cutoff defined as the control mean plus 3 or 4 SD
had a positive correlation between the two parameters.
As an anticoagulant protein, ANX A5 also inhibits
activated thrombocytes aggregation or their fusion with
tissue factor-bearing microvesicles [3]. Our total SLE
group showed a weak positive correlation between plasma
ANX A5 and thrombocyte count per unit blood volume.
The correlation coefficient was very high in the SLE sub-
group with the level of ANX A5 over the control mean plus
4 SD, and it was moderate in the subgroups with concen-
tration of ANX A5 above the control mean plus 1–3 SD. It
might be hypothesized that these relationships result from
an anti-aggregation effect of plasma ANX A5 on throm-
bocyte, which, from the clinical point of view, could be
beneficial in SLE patients. Our investigations did not reveal
ANX A5 plasma concentration [ng/mL]
Thr
ombo
cyte
s bl
ood
coun
t [x
109 p
er L
]
100
150
200
250
300
350
400
450
ANX A5 plasma concentration [ng/mL]
Thr
ombo
cyte
s bl
ood
coun
t [x
109 p
er L
]
100
150
200
250
300
350
400
450
ANX A5 plasma concentration [ng/mL]
Thr
ombo
cyte
s bl
ood
coun
t [x
109 p
er L
]
100
150
200
250
300
350
400
450
ANX A5 plasma concentration [ng/mL]
Thr
ombo
cyte
s bl
ood
coun
t [x
109 p
er L
]
100
150
200
250
300
350
400
450
r = 0.2372 r = 0.3268
r = 0.3901 r = 0.4223
a b
c d
ANX A5 plasma concentration [ng/mL]
0 1 2 3 4 5 60 1 2 3 4 5 6
0 1 2 3 4 5 60 1 2 3 4 5 6
0 1 2 3 4 5 6
Thr
ombo
cyte
s bl
ood
coun
t [x
109 p
er L
]
100
150
200
250
300
350
400
450r = 0.7670
e
Fig. 2 Correlations between
plasma ANX A5 concentration
and peripheral blood
thrombocyte count in a total
group of SLE patients and b c de subgroups with SLE identified
as the arithmetic mean of ANX
A5 concentration in the control
plus 1–4 standard
deviations (SD)
1340 Rheumatol Int (2012) 32:1335–1342
123
significant correlations between plasma ANX A5 and
APTT, prothrombin time, and INR both in the total SLE
group and in SLE subgroups with an ANX A5 cutoff
defined as the control mean plus 1–4 SD.
As it was mentioned earlier, we obtained significantly
higher IgG aANX antibodies levels in the plasma of the
total SLE group and in the subgroup on immunosuppres-
sive therapy compared with the control. The phenomenon
had been previously investigated [1], and the results of our
investigations are partly consistent with the observations of
other authors [23, 24], who revealed that these antibodies
were more frequently expressed in patients with thrombotic
complications of SLE and suggested that these antibodies
had LA properties [24]. Our studies have revealed a weak
negative correlation between plasma IgG aANX antibodies
levels and APTT in the whole SLE group. This seems to
contradict LA properties of aANX antibodies since LA
typically leads to APTT elongation in vitro and pro-
thrombotic tendency in vivo. As already mentioned, the
pathogenic role of aANX antibodies in humans has not
been fully clarified yet [1]. Differences between our results
and those of other authors [25] might reflect the lack of
standardized tests, use of different-specificity reagents, or
the fact of study parameters being determined in serum or
plasma samples [24, 26].
We conclude that in SLE patients, the annexinopathy
does exist, and it could be suggested that, in patients treated
for mild-to-moderate SLE, elevated plasma ANX A5 level
and IgG aANX A5 antibodies concentration are associated
with the severity of the disease. The obtained results
indicate that the role of aANX A5 and IgG CL antibodies
should be taken into consideration as causative factors of
the increased plasma ANX A5 levels. The relationships
between plasma ANX A5 level and the peripheral blood
thrombocyte count were revealed. Noticeable negative
correlation between IgG aANX A5 antibody levels with
APTT in the total SLE group seems to contradict the
suggested LA properties of these antibodies. The observed
connection between plasma ANX A5 level and serum
cholesterol concentration deserves further exploration.
These data and their possible advantages for the diagnosis,
management, and prognosis in SLE require further ran-
domized clinical studies carried out on larger groups of
untreated and treated patients with SLE.
Conflict of interest The authors declare that they have no conflict
of interest.
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