Decreased Circulating Level of Soluble Glycoprotein ... - EuroJournals

American Journal of Scientific Research 

ISSN 1450-223X Issue 26(2011), pp.59-73 

© EuroJournals Publishing, Inc. 2011 

http://www.eurojournals.com/ajsr.htm 

Decreased Circulating Level of Soluble Glycoprotein-130 in 

Recurrent Miscarriage Patients 

Kambiz Bagheri 

Corresponding Author, Department of Immunology, Faculty of Medicine 

Kazerun Branch, Islamic Azad University, Kazerun, Iran 

E-mail: Bagheri_kbz@yahoo.com or kbz.bagheri@gmail.com 

Tel: 0098-711-8323702 or 0098-9173118066; Fax: 0098-711-8208671 

Padideh Ebadi 

Department of Biochemistry, Faculty of Medicine, Kazerun Branch 

Islamic Azad University, Kazerun, Iran 

Hossein Berenjeian Tabrizi 

Department of Physical Education and Sport Sciences 

Kazerun Branch, Islamic Azad University, Kazerun, Iran 

Aboozar Dehghan 

Department of Clinical Studies, School of Veterinary Medicine, Kazerun Branch 

Islamic Azad University, Kazerun, Iran 

Abstract 

Recurrent miscarriage occurs in 1–3% of women which approximately 50% of its 

cases remain unexplained. It is revealed that the immune system may be implicated in 

miscarriage. Soluble glycoprotein-130 (sgp130) as a natural inhibitor of interleukin-6 (IL- 

6) mediated responses has been shown to suppress several inflammatory responses. In this 

study, 50 variables containing socio-demographics, health-related habits, depression score, 

serum molecules and blood parameters besides the sgp130 level were evaluated in recurrent 

miscarriage women with at least three previous abortions and healthy women with natural 

childbirth (normal multigravida control) in order to evaluate sgp130 which might have a 

role in some abortions. We found that although there was no significant difference in their 

socio-demographics, physical activity, educational level, dietary habits, smoking or alcohol 

consumption, depression score and its prevalence in these patients was higher than controls. 

Our results showed that the patients had significantly lower level of sgp130 than controls 

which also remained significant after adjustment for other variables. Although there were 

no significant differences in their routine hematological parameters, our recently aborted 

patients had averagely higher post-abortion antinuclear-antibody (ANA) than the controls. 

None of studied parameters in miscarriage-patients, except the level of anti-annexin-V 

antibodies (Anti-AV) and depression score were correlated with sgp130 level. Moreover, 

there was a positive correlation between hookah consumption and depression status of 

patients. A positive significant correlation was also found between the number of abortions 

and parameters such as age, partial-thromboplastin-time (PTT), C-reactive-protein (CRP) 

and rheumatoid-factor (RF) in patient group. The patients’ level of anti-double-stranded 

DNA antibodies (anti-dsDNA) as well as RF was correlated positively with depression

Decreased Circulating Level of Soluble Glycoprotein-130 in Recurrent Miscarriage Patients 60 

score. Taken together, as a new result, we concluded that the changes of some blood 

parameters like the lower post-abortion level of sgp130 or higher level of some 

autoimmune markers along with a higher depression score may be associated with recurrent 

spontaneous miscarriage. Further studies are needed to determine whether the discussed 

changes in our parameters are a cause of, or merely a consequence of abortion event or 

even abortion-related depression. Thus we can summarize by saying that psychological 

problems, inflammation and autoimmune processes may be associated with each other and 

with recurrent miscarriage. 

Keywords: Soluble glycoprotein-130, Recurrent miscarriage, Autoantibody, Depression 

1. Introduction, Objectives and Aims 

Recurrent miscarriage is often defined as three or more consecutive miscarriages which occur in 1–3% 

of women. Recurrent miscarriage is a heterogeneous condition and approximately 50% of them remain 

unexplained. There are still many unresolved questions about its cause and treatment (Carrington, 

Sacks, & Regan, 2005). This recurrent loss of pregnancy is often distressing for the patients and 

frustrating for physicians. Recurrent miscarriage causes significant psychosocial morbidity, and for 

many couples the label of ‘unexplained’ is unacceptable. Overall, 75% of affected women will have a 

successful subsequent pregnancy, but this rate falls for older mothers and with increasing number of 

miscarriages (Duckitt & Qureshi, 2008). The immune system has long been implicated in miscarriage. 

It is revealed that the level of inflammatory mediators may be as factors related to pregnancy 

complications including recurrent miscarriage. So far, several investigations have been conducted on 

the relationship between the IL-6 family members or other related molecules and the natural processes 

associated with fertility and pregnancy (Arruvito, Billordo, Capucchio, Prada, & Fainboim, 2009; 

Arslan, et al., 2004; Hattori, et al., 2007). On the other hand, there are some studies which show that 

most women with habitual abortion of unknown etiology have a higher level of autoreactivity, which 

may affect the course of pregnancy. Indeed, there are several evidences which help us to confirm the 

association of autoimmune and psychological problems. Moreover, in the respect of inflammation, 

available evidence is consistent with three causal pathways: depression to inflammation, inflammation 

to depression, and bidirectional relationships (Howren, Lamkin, & Suls, 2009). For example, an 

activation of inflammatory response may occur in depression (Maes, et al., 1997; Song, et al., 1998). 

Thus, we can summarize by saying that inflammation and autoimmune processes may be 

associated with abortion and on the other hands, both processes of autoimmune and inflammation is 

known that can be associated with depression and psychological problems. Also, other factors such as 

coagulation disorders, blood sugar and homocysteine (Hcy) level related problems can also be effective 

in causing abortion. In this regard, some other factors related to socio-demographic information or 

health-related lifestyle habits are noteworthy and thus their assessment in miscarriage patients could be 

helpful. 

It will be interesting to simultaneously evaluate the relationship between three major 

components which mentioned above (i.e., inflammation, autoimmunity and depression) along with the 

socio-demographic and health-related lifestyle information in miscarriage patients. 

Therefore, sgp130 as a natural inhibitor of IL-6 mediated inflammatory responses was selected. 

CRP was also studied as another inflammatory marker. Probable abortion related autoimmune markers 

were including ANA, anti-dsDNA, anti-AV, anti-laminin-1, anticardiolipin antibodies (aCLA), lupus 

anticoagulants (LACs) and RF. Depression was assessed with the Beck's depression Inventory (BDI). 

Socio-demographics and health-related lifestyle habits were also comprised of 27 separate components. 

sgp130 as a natural inhibitor or antagonist of IL-6 / soluble IL-6 receptor (sIL-6R) complex 

contributes to resolution of acute inflammatory response and also transition between acute and chronic 

inflammatory reaction (Augustyniak, Majkowska-Skrobek, Basiewicz-Worsztynowicz, & Jankowski,

61 Kambiz Bagheri, Padideh Ebadi, Hossein Berenjeian Tabrizi and Aboozar Dehghan 

2006). Indeed, sgp130 selectively inhibits IL-6 trans-signaling and thus is the natural inhibitor of IL-6 

responses dependent on sIL-6R (Jostock, et al., 2001). 

The main purpose of this study was to test if recurrent miscarriage is associated with a different 

level of sgp130 after adjusting for other variables. As well as, in this study the relationship between 

many factors such as socio-demographic information, health-related lifestyle habits, history of 

pregnancy loss or abortion, depression status, the level of several autoantibodies, some coagulation 

parameters, the level of Hcy, glucose challenge test (GCT), fasting blood sugar (FBS), CRP and RF 

with themselves and with sgp130, has been evaluated. 

2. Research Materials and Methods 

2.1. Miscarriage Patients and Control Group 

We studied 42 unrelated recurrent miscarriage women with at least three previous abortions which 

were not under therapy. Some exclusion criteria were hematological malignancies, viral infections, 

pulmonary disorders and documented sepsis. 42 healthy age matched women with natural childbirth 

(normal multigravida control) were also randomly selected as controls. The healthy controls were free 

of any acute and chronic disease or apparent illnesses and also any history of psychiatric diseases or 

pregnancy loss. Informed consent was obtained from all the participants. 

2.2. Detection of ANA and Anti-dsDNA Antibody 

The presence of ANA and anti-dsDNA antibodies was determined by ELISA (Aesku.lab, Aesku 

Diagnostics, Wendelsheim,Germany). 

2.3. Detection of Anti-AV and Anti-Laminin-1 Antibodies 

Levels of circulating IgG/IgM antibodies directed against annexin V as well as IgG antibodies against 

laminin-1 were determined by their respective ELISA kit (Aesku.lab, Aesku Diagnostics, 

Wendelsheim,Germany). 

2.4. Total Hcy Level Measurement 

Fasting total plasma L-homocysteine was measured by Axis® Homocysteine enzyme Immunoassay kit 

(Axis-Shield Diagnostics Ltd., The Technology Park Dundee DD2 1XA. United Kingdom). All 

samples were run at the same time to minimize assay variability. 

2.5. Detection of Serum CRP and RF 

The acute-phase inflammatory response was assessed by determining the serum level of CRP in a highsensitive 

approach (HS-CRP) by photometry method (Dade Behring, Deerfield, USA). The serological 

status for RF was performed using a latex semi-quantitative kit (ENiSon, ENiSon Lab, Tehran, Iran). 

2.6. Detection of aCLA 

Plasma concentration of aCLA were performed using the standard aCL ELISA kit (Orgentec 

Diagnostika GmbH, Mainz, Germany), which recognises the sum of IgG, IgM and IgA class anti- 

Cardiolipin autoantibodies. 

2.7. Measurement of LAC 

All patient samples were measured with the “classic” LAC assays, notably a partial thromboplastin 

time – lupus anticoagulant (PTT-LA) (PTT-LA kit, Diagnostica Stago, Asnieres, France). LACs are 

antibodies detected based on their ability to prolong phospholipid dependent coagulation reactions.


Indeed lupus anticoagulants exert an inhibitory effect on phospholipids, which are normally required in 

some clotting tests such as activated partial thromboplastin time (APTT). The presence in the test 

plasma of lupus anticoagulants prolongs the clotting time. 

2.8. Coagulation Tests 

Functional protein S and C levels were measured using the STA®-Staclot® Protein S kit and C kit 

(Diagnostic Stago, France) according to the manufacturer’s instructions. Antithrombin activity (AT) 

level in plasma was quantitated using the STA®-Stachrom® AT III kit (Diagnostic Stago, France) by a 

synthetic chromogenic substrate method. Prothrombin time (PT) was also measured using the 

NEOPLASTIN® CI kit (Diagnostic Stago, France). The result of the PT test was reported as the 

international normalized ratio (INR) which is the ratio of a patient’s prothrombin time to a normal 

control sample. 

2.9. Measurement of FBS and GCT Value 

FBS test were done on fresh samples. But GCT value was noted from medical records of patients, 

which had been performed between the 24th and 28th weeks of gestation. 

2.10. Hematological Studies 

A complete blood count (CBC) with differential was done on the hematology counter (Coulter Sysmex 

K1000 machine). ESR was also measured by Westergren method. 

2.11. Assessment of Depression Status 

Depression score was measured using the Persian translated and validated version of the BDI 

(Ghassemzadeh, Mojtabai, Karamghadiri, & Ebrahimkhani, 2005), the suggested cut-off values of 

which are classified in table 1. The BDI-(Persian) contained a full 21-item, self-report questionnaire, 

which the severity of each item, scores between 0 (indicating no depressive symptomatology) and 3 

(indicating a severe level of symptomatology), with possible total scale score ranging from o to 63. 

Table 1: Suggested classified cut-off values for the BDI assessment 

Test scores Depression status Alphabetical grouping 

0-10 No depression A 

11-16 Mild depression B 

17-20 

Mild to moderate depression-require consultation with the 

C 

psychologist 

21-30 Moderate depression D 

31-40 Severe depression E 

41-63 Severe depression-require hospitalization F 

Information on depressed mood and the intensity of depression in the recruited subjects was 

obtained using the BDI-Persian. A score of 17 and more indicates a clinically significant depression. 

2.12. Questionnaires 

A team of interviewers, who received training, completed questionnaires consisting of variables, all of 

which were defined as quantitative values (Table 2). All the discussed variables in the questionnaires 

along with all the measured factors and laboratory parameters were 50 variables.


2.13. Measurement of Sgp130 Level 

The serum sgp130 levels were assessed in triplicate by a commercial human specific sandwich ELISA 

kit (Quantikine, R&D Systems Inc, Minneapolis, MN, USA), according to the manufacturer’s 

guidelines. The detection limit of the sgp130 ELISA was less than 0.05 ng/ml. 

2.14. Statistical Analysis 

The statistical significant of differences between cases and controls were calculated by the 

independent-samples T test and the differences at p values


r= -0.321, p=0.038) even after controlling for their age and body weight, so that more depressed 

patients had a lower level of sgp130. 

Partial correlation analysis with the control of age and weight in our study showed that there is 

a positive independent correlation between hookah consumption and depression status of recently 

aborted women (Figure 2D, r= +0.398, p=0.009). Thus, our obtained results showed that depression of 

these patients has a direct association with some habits like hookah consumption. 

A positive significant correlation was found between the number of abortions and parameters 

such as age (Figure 2E, r= +0.468, p=0.002), partial-thromboplastin-time (PTT) (Figure 2G, r= -0.348, 

p=0.024), C-reactive-protein (CRP) (r= +0.519, p=0.00) and rheumatoid-factor (RF) (r= +0.586, 

p=0.00) in patient group. 

We also found that a significant higher gestational glucose-challenge-test (GCT) value is 

observed in our patients recorded histories (Figure 1C, p


The independent samples T test and the Chi-square test were used to analyze our data in the 

study and to evaluate the significance of the difference between the two groups. P values >0.05 were 

considered as non-significant (NS) and p values


Figure 2: Some of the important relationships between patient variables illustrated by scatter plots 

Scatter plots was drawn and overlaid with fitted regression lines (with 95% confidence 

intervals) to illustrate how the plotted parameters were positively or negatively correlated. All of the 

above significant correlations were still significant after adjustment for covariates. 

4. Discussion 

The sgp130 is the natural inhibitor of trans-signaling mediated by the soluble IL-6/IL-6R complex 

which has been shown to suppress several inflammatory responses. 

50 variables containing socio-demographics, health-related habits, depression, serum molecules 

and blood parameters besides the sgp130 level were evaluated in recurrent miscarriage women with at 

least three previous abortions and healthy women with natural childbirth in order to evaluate sgp130 

which might have a role in some abortions. 

Our results showed that patients with recurrent spontaneous miscarriage have significantly 

decreased plasma levels of sgp130 compared to those with normal. Correlation analysis between 

sgp130 level and all other variables in our patient group showed that the level of this natural inhibitor 

of IL-6 responses has a negative correlation with depression status and also the level of anti-AV even 

after controlling for their age and body weight. Some evidences suggested that anti-AV antibodies may 

be associated with recurrent pregnancy losses (Matsubayashi, et al., 2001). 

The sgp130 is a natural inhibitor of IL-6 mediated inflammatory responses. There are several 

studies on the relationship between the IL-6 family members and pregnancy (Arruvito, et al., 2009; 

Arslan, et al., 2004; Hattori, et al., 2007). The immune system contributes to the outcome of pregnancy 

by complex immunological interactions. For example, T helper 1 (Th1) cytokines TNF-alpha and IFNgamma 

could cause inflammation and together are thought to threaten the maintenance of pregnancy 

(Knackstedt, et al., 2003). Some evidences support a role of the immune system in the first trimester 

pregnancy and hypothesize that missed abortion may be associated with an enhanced Th1 reactivity, 

whereas threatened abortion with good outcome resembles the normal pregnancy with a non-enhanced 

Th1 reactivity (Paradisi, Porcu, Venturoli, Maldini-Casadei, & Boni, 2003). It is shown that IL-6 

produced not only by immunocompetent cells such as macrophages and mast cells, but also by 

trophoblasts and decidua cells, is directly involved in the pathology of abortion (Zenclussen, et al., 

2003). It has been proposed that serum TNF-alpha and IL-6 could be related to the pregnancy loss


(Arslan, et al., 2004). Some other authors found significant differences between IL-6 levels in nonpregnant 

recurrent spontaneous miscarriage women before and after lymphocyte immunotherapy and 

showed that the alloimmunization with paternal white cells leads the serum IL-6 and sIL-6R levels to 

the values observed in the course of normal pregnancy (Zenclussen, Kortebani, Mazzolli, Margni, & 

Malan Borel, 2000). Moreover it has been revealed that both IL-6 and IL-8 in cervical mucus collected 

at 4-5 weeks' gestation are significantly higher in patients who have a history of two or more 

unexplained consecutive first trimester miscarriages and aborted subsequently than in those who had a 

live birth and thus might have predictive value for cases of recurrent miscarriage (Hattori, et al., 2007). 

It is also reported that in comparison with fertile women, those with recurrent spontaneous abortion 

show significantly increased levels of sIL-6R and IL-6 (Arruvito, et al., 2009). In addition to abortion 

process, theses cytokines may also involve in infertility or some other reproductive failures. For 

example, altered secretion of sgp130 may be observed in patients with primary unexplained infertility. 

The sgp130 secretion is greatly increased during a normal menstrual cycle and infertile patients show 

reduced secretion of sgp130 compared with fertile controls (Sherwin, Smith, Wilson, & Sharkey, 

2002). Other results suggest that the balance between sgp130 and its membrane-bound form may play 

an important role in regulating cytokine action necessary for blastocyst implantation (Classen-Linke, 

Muller-Newen, Heinrich, Beier, & von Rango, 2004). IL-6 and sIL-6R may also contribute to the 

pathogenesis of endometriosis-associated infertility (Yoshida, et al., 2004). Polycystic Ovary 

Syndrome (PCOS) as other cause of female infertility, are characterized by an increased sgp130 

(Nikolajuk, et al.). It is also reported that serum sIL-6R and sgp130 levels could be related to the 

development of pregnancy induced hypertension (Y. Li, Wang, & Qi, 2001). According to another 

study, IL-2 and IL-6 levels are significantly higher in women with pre-eclampsia as compared to those 

of healthy pregnant women (Dimitrakova, Milchev, Batashki, & Karumanchi, 2007). 

All the above reports, confirmed our observations about the lower post-abortion level of sgp130 

in recurrent miscarriage women. Indeed, the reduced levels of sgp130 as a natural inhibitor of IL-6 

responses cause changing the balance of IL-6 related network in these women and thereby could be 

related to spontaneous abortion and might have predictive value for some cases of recurrent 

miscarriage. Our reported serum values for sgp130 in patients and controls in this study are consistent 

with those reported by other researchers for some people with relatively similar conditions (Giuliani, et 

al., 2001; Y. Li, et al., 2001). 

There are some reports that the sgp130 level was not significantly different in the blood of 

pregnant and non-pregnant women. On the other hand, matching the time sampling of all pregnant 

women was a problem for us. Also, it is clear that the final outcome of a pregnancy is not known until 

the end of period. Thus we decided that examine the levels of sgp130 in recurrent miscarriage women 

with at least three previous abortions and healthy women with natural childbirth. 

Our study about the several autoantibodies in miscarriage patients lead also to some interesting 

results. We found that beside the higher level of ANA in these women, more depressed patients had 

higher level of anti-dsDNA and RF. We also found that women who had greater frequency of abortions 

had higher level of CRP and RF. 

There are some studies which show that most women with unexplained habitual abortion have a 

higher level of autoreactivity. For example, the incidence of anti-smooth muscle antibody in women 

with habitual abortion of unknown etiology is increased compared with normal multigravida control 

(Q. Li, Li, & Tian, 1998). In a previous study using western blotting the women with primary 

unexplained infertility and those with secondary unexplained recurrent miscarriage had a significantly 

higher prevalence of autoantibodies (el-Borai, et al., 1988). A first early pregnancy loss may be 

associated with increased levels of several autoantibodies (Gris, et al., 2003). It is also reported that in 

women with autoimmune disorders, a history of recurrent pregnancy loss is independently associated 

with reactivity against three distinct Ro antigen-related reactivities (Ro52, Ro60, p57) and also with the 

presence of antithyroglobulin antibodies, suggesting that cumulative autoimmune responses against 

these non-organ-specific and organ-specific antigens correlate with the risk of stillbirth and 

spontaneous abortion (Mavragani, Ioannidis, Tzioufas, Hantoumi, & Moutsopoulos, 1999). Some other


evidences indicate that antiphospholipid antibodies which are a family of autoantibodies including 

lupus anticoagulant and anticardiolipin, induce thrombosis and pregnancy complications including 

recurrent stillbirth, recurrent miscarriage, pre-eclampsia and intra-uterine growth retardation (Chamley, 

1997). The results of previous studies indicate that human aCL IgG that are beta2-GPI independent can 

induce placental necrosis and fetal loss in BALB/c mice (Ikematsu, et al., 1998). Recent evidence 

shows that anti-AV and anti-beta2-GPI antibodies should be regarded as independent risk markers 

(Zammiti, et al., 2006). Recently, it is reported that the presence of IgG anti-laminin-1 antibodies in the 

blood is significantly associated with recurrent first-trimester miscarriages and subsequent negative 

pregnancy outcomes. Thus, anti-laminin-1 antibodies may be important in the development of 

autoimmune-mediated reproductive failures (Inagaki, Kondo, Lopez, Shoenfeld, & Matsuura, 2005). 

Some results have been shown that women with recurrent spontaneous abortion of unknown etiology 

are differed in some parameters of immune response such as higher incidence of antinuclear antibodies 

in comparison with nonpregnant normal multigravidas (Malinowski, et al., 1997). There are some 

reports about the presence of ANA+ serum in abortion cases (Kano, Shimizu, & Kanda; Ticconi, et 

al.). Based on a previous study, the frequency of positive tests for ANA was significantly higher in 

Kuwaiti patients with unexplained recurrent spontaneous abortions (13.6%) than in controls (1.2%). 

No difference was found between first and second trimester aborters in the frequency of ANA positive 

tests. However, secondary aborters had significantly higher frequency of ANA (Bahar, Alkarmi, 

Kamel, & Sljivic, 1993). In other study on the prevalence of ANA in healthy women with first 

trimester recurrent spontaneous abortion, it was reported that only 13.2% of them had low levels of 

antinuclear antibodies, none of which were specific. Thus the reported prevalence of ANA in these 

group was low (Eroglu & Scopelitis, 1994). But another study reported a high prevalence of ANA in 

the patients with habitual abortion (30%) as compared with the control group (6.6%) (Garcia-De La 

Torre, Hernandez-Vazquez, Angulo-Vazquez, & Romero-Ornelas, 1984). One recent study in 2010 

reported that ANA could be of some value in identifying women with recurrent pregnancy loss (RPL) 

with potential, although still not fully defined, immune abnormalities. It was reported that antinuclear 

antibodies at titers >/= 1:80 were detected in 50% women with RPL and in 16% control women. 

Elevated ANA titers (>/=1:180) were detected only in RPL women, whereas all control women had 

ANA titers no greater than 1:80. No differences in ANA positivity could be detected according to the 

type (primary or secondary) or number (>2 versus >/=3) of losses (Ticconi, et al.). According to a 

study about the outcome of pregnancy in ANA positive women, the perinatal mortality rate in the 

ANA-positive group was 18.6%, while there were no perinatal deaths in the ANA-negative control 

group. But ANA titer did not also correlate with the outcome of the pregnancy (Kiuttu, Hartikainen, 

Makitalo, & Ruuska, 1994). In other study results demonstrated a high prevalence of low-titer ANApositive 

serum in patients with both explained (34.3%) and unexplained (51.5%) pregnancy losses in 

compare with healthy pregnant (6.8%) and nonpregnant women (5.6%) (Malinowski, et al., 1994). A 

review of pregnancy outcome by another study indicated that maternal antinuclear antibodies are not, 

in general, associated with abnormalities of the pregnancy or of the offspring (Rosenberg, Bingham, & 

Fong, 1986). In a more recent study on the Argentine women, there was also no significant difference 

between the prevalence of ANA in fertile controls and patients with recurrent pregnancy loss with 

ANA (Bustos, et al., 2006). In other report it was demonstrate that women with recurrent spontaneous 

abortions showed significantly higher incidence of antibodies to phospholipids than normal 

multigravida controls. In contrast, the incidence of antibodies to polynucleotides and histones was not 

different between these two groups (Kwak, Gilman-Sachs, Beaman, & Beer, 1992). 

All these mentioned evidences could help us to confirm the higher level of autoreactivity in our 

miscarriage patients. 

There are some evidences which help to confirm our results regarding to higher score and 

prevalence of depression in miscarriage patients. For example it is reported that abortion may be a risk 

factor for subsequent depression in the period of 8 years after the pregnancy event (Cougle, Reardon, 

& Coleman, 2003). A number of studies have discussed about the relationship between abortion and 

depression (Rees & Sabia, 2007). For example in one report, the depression score for recurrent


miscaririag women and non-miscarriage group was 27.6+/-8.8 and 19.4+/-7.1 respectively (Andalib, 

Rezaie, Oreizy, Shafiei, & Baluchi, 2006). 

Our study about the depression status of miscarriage patients lead to some interesting results. 

We found that beside the higher average of depression score in these women, more depressed patients 

had higher level of anti-dsDNA and RF but lower level of sgp130. Also surprising that, more depressed 

patients, averagely more smoke hookah but had not more abortion number. 

Taken together these results showed that the lower post-abortion level of sgp130 or higher level 

of some autoimmune markers may become simply a consequence of higher depression which in turn 

may be related to unpleasant abortive occurrence or some habits like hookah consumption. 

Indeed high level of several autoantibodies like ANA or anti-dsDNA as well as CRP or RF in 

some miscarriage cases may be an outcome of depression which resulting from recurrent miscarriage 

as one of the most horrible event of women's life. 

There are several reports about the association of psychological disorders and autoimmune 

processes. For example it is reported that Immune dysregulation is common in depressive patients and 

also depressive symptoms have been found at a high prevalence in autoimmune disease. Recent studies 

have found that autoantibodies play an important role in the pathogenesis of depression both in animal 

models and human. It is suggested that depression can be regarded as autoimmune disease caused by 

various autoantibodies (Chen, Jiang, Ouyang, & Chen, 2009). For example it is believed that 

postpartum depression may have an autoimmune etiology (Gleicher, 2007). Major depression may be 

also accompanied by systemic immune activation or an inflammatory response with higher 

autoantibody (antinuclear, antiphospholipid) titers (Maes, 1995). Some groups had also reported higher 

titers of autoantibodies in depressed subjects than in normal controls. Meanwhile those observations 

pointed towards a higher expression of antiphospholipid antibodies during depression but a much 

lower incidence of positive patients than in classical autoimmune disorders, such as SLE (Maes, et al., 

1993). It is also reported that in the patients with major depression, the frequency of some elevated 

autoantibodies like ANA are significantly higher than in the control group. In addition, in the 

schizophrenic patients significantly more often showed increased levels of ANA. These results point 

towards the existence of an unspecific autoimmune disposition or reaction in at least a subgroup of 

patients with major depression and schizophrenia (Laske, et al., 2008). 

Our results about the lower post-abortion level of sgp130 as a probable consequence of their 

higher depression are along with the previous evidences. 

For example, it is showed that elevated circulating pro-inflammatory cytokines are associated 

with symptoms of depression, and disorders involving chronic inflammation are often co-morbid with 

major depression (Dhabhar, et al., 2009). Some evidence also indicates that an immune response with 

an increased production of proinflammatory cytokines often accompanies major depression. 

Indeed, depression and IL-6 are positively associated in clinical and community samples 

(Howren, et al., 2009). Some other evidences suggest that there is an activation of the immuneinflammatory 

response system in depression. For example it is reported that serum IL-6 are 

significantly higher in subjects with major depression than in normal controls (Maes, et al., 1997; 

Song, et al., 1998). It was hypothesized that the elevated IL-6 levels during the acute state of 

depression or schizophrenia may reflect an unspecific stress response (Frommberger, et al., 1997). 

Although, other study showed that IL-6 and the sIL-6R are decreased in cerebrospinal fluid of geriatric 

patients with major depression. In this study, the level of sgp130 had no statistically significant 

difference between patients and controls (Stubner, et al., 1999). Other new study indicates an 

association between increased levels of IL-6 with depressive symptomatology in elderly individuals 

(Dimopoulos, Piperi, Psarra, Lea, & Kalofoutis, 2008). New evidences suggest that higher plasma IL-6 

activity is associated with the refractoriness of depression (Yoshimura, et al., 2009). Recently, It has 

been also revealed that depression in cancer is associated with increased plasma IL-6 concentrations 

(Jehn, et al.). Moreover, a direct correlation between BDI (symptoms of depression) and IL-6 levels 

has been found in other patients such as those on maintenance haemodialysis (Hung, et al.).


Thus, all these evidences could confirm which lower sgp130 in patients may be a probable 

consequence of their higher depression. 

5. Summary and Concluding Remarks 

Taken together, indeed, as a new result, we found that the changes of some blood parameters like the 

lower post-abortion level of sgp130 or higher level of some autoimmune markers along with a higher 

depression score may be associated with recurrent spontaneous abortion. To our knowledge, this study 

is also relatively novel in that it simultaneously examines the relationship between serum sgp130 levels 

in recurrent miscarriage patients and their autoantibody titers, some coagulation parameters, the level 

of Hcy, GCT, FBS, CRP and RF as well as the socio-demographic, psychological, environmental, 

dietary, laboratory, smoking and lifestyle parameters all of which were intelligently defined as 

quantitative values. 

Further studies are needed to determine whether the discussed changes in our parameters are a 

cause of, or merely a consequence of their abortion event or even abortion-related depression. Further 

studies are also required to justify the role of sgp130 in recurrent miscarriage. 

Thus we can summarize by saying that psychological problems, inflammation and autoimmune 

processes may be associated with each other and with recurrent abortion. 

Hopefully, these additional information and knowledge provided will, before long, lead to more 

successful treatment and improved outcome in miscarriage women. 

Acknowledgments 

The authors would like to thank Islamic Azad University, Kazerun Branch for their financial and other 

support as well as Dr. Parvin Javad Baghdasar (from Molavi clinical Laboratory, Shiraz, Iran), for her 

assistance with data collection and patient referrals. 

Conflict of interest: None declared. 

References 

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