Levels Of Antiphospholipid Antibodies Research Articles

Abstract 461: Antiphospholipid Antibodies In Covid-19 Convalescent Plasma

Background: Although convalescent plasma has historically yielded significant benefits in the treatment of infectious diseases, numerous clinical trials have not shown a consistent benefit in treating either moderately or severely ill COVID-19 patients with plasma from convalescent patients. We previously reported increased levels of antiphospholipid antibodies (aPL) in acutely ill COVID patients, with high aPL titers correlating with more neutrophil extracellular traps (NETs) and poorer patient outcomes. We hypothesized that persistence of potentially deleterious autoantibodies in previously hospitalized, convalescent plasma donors may activate immune cells and add context for the lack of clinical efficacy in COVID. Methods: 116 samples of convalescent plasma from donors previously hospitalized with COVID were obtained from Vitalant. Antibody titers (IgG, IgM, IgA) of anti-2-glycoprotein 1 (a2GP1) and anti-cardiolipin (aCL) and anti-phosphatidylserine/prothrombin (IgG, IgM) were quantified. NET formation by healthy human neutrophils treated with convalescent plasma was evaluated in vitro. Results: High aPL titers >40 U/mL) were observed in 10/116 (8.6%) convalescent samples, and 6/10 were positive for either IgG or IgM aCL. The aPL positivity rate exceeded the expected background population rate of ~3%. Six of 116 convalescent samples increased NET-associated MPO activity in purified, primary neutrophils from healthy donors compared with control plasma (mean increase of 23% +/- 11, p<0.01), where only 2 of these were aPL-positive samples. Conclusion: aPL were elevated in a larger proportion of surveyed convalescent plasma samples than reported in the healthy population. aPL positivity did not correlate with purified neutrophil activation, suggesting aPL in donor plasma does not have a direct, activating effect on healthy neutrophils. Considering the complex interactions among circulating blood cells, ongoing experiments are examining the impact of convalescent plasma on platelet and endothelial cell function to further elucidate potential autoantibody-mediated vascular perturbations. The results of these studies will be important in informing the vascular implications and safety of convalescent plasma in COVID.

A case of primary antiphospholipid antibody syndrome with intermittent cerebral venous sinus thrombosis manifested with recurrent epilepsy

Antiphospholipid syndrome (APS) is an acquired autoimmune clinical disorder characterized by persistently raised levels of anti-phospholipid antibodies and clinical feature of hypercoagulability (recurrent vascular thrombosis and pregnancy morbidities). Primary APS is idiopathic in nature though secondary APS is associated with other connective tissue diseases like SLE. Here, we present an instance of primary APS with recurrent cerebral venous sinus thrombosis in a youthful unmarried female who clinically presented with generalized epilepsy. Level of anti-cardiolipin (aCL) and anti-beta 2 GP1 antibodies were found elevated on two occasions 12 weeks apart. The patient was treated with anticoagulation therapy along with anti-epileptic therapy and she responded well to the therapy. This case report highlights that clinicians should always suspect APS in female patients who had history of seizures and ischemic or thrombotic lesions on brain imaging, irrespective of presence of pregnancy comorbidities. Keywords: antiphospholipid syndrome; cerebral venous; sinus thrombosis; epilepsy

Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps.

BackgroundPolyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti‐phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS).ObjectiveTo compare APA levels (anti‐cardiolipin, anti‐phosphatidylethanolamine (anti‐PE), and anti‐β2‐glycoprotein (anti‐B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti‐dsDNA IgG and markers of coagulation.MethodsPatient specimens were assayed for APA IgG, anti‐dsDNA IgG and thrombin‐anti‐thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical‐mechanical coagulometer.ResultsAnti‐cardiolipin IgG in NP was 5‐fold higher than control tissue (p < .0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 µg/mL (36.7 s vs. 33.8 s, p = .024) and 600 µg/mL (40.9 s vs. 34.7 s, p = .0037). Anti‐PE IgG antibodies were increased in NP (p = .027), but anti‐B2GP IgG was not significantly higher (p = .084). All APAs correlated with anti‐dsDNA IgG levels, which were also elevated (R = .77, .71 and .54, respectively, for anti‐cardiolipin, anti‐PE, and anti‐B2GP; all p < .001), but only anti‐cardiolipin (R = .50, p = .0185) and anti‐PE (R = 0.45, p = .037) correlated with TaT complex levels.ConclusionsAPA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti‐coagulant activity similar to those observed in anti‐phospholipid syndrome, suggesting that they may have pro‐coagulant effects in polyp tissue.

The clinical significance of antiphospholipid antibodies in COVID-19 infection.

One of the factors that may aggravate the clinical presentation in COVID-19 is the increased level of antiphospholipid antibodies (aPLs) and thrombotic events that can be seen with the disease. In our retrospective study, we aimed to evaluate the effect of aPLs on the clinical findings in patients with a diagnosis of COVID-19. Seventy-three patients diagnosed with COVID-19 and examined for aPLs were included in the study. Patients were divided into two groups according to the test results of aPLs. Clinical and laboratory parameters were compared in both groups to reveal whether there was any difference between the groups. There were 15 patients with a positive aPLs test. Dyspnea, nausea, vomiting, myalgia, and abdominal pain were significantly higher in the aPLs positive group than those with negative aPLs. The duration of hospital stays and the need for oxygen therapy of the patients in the aPLs positive group were significantly higher than the aPLs negative group. However, no difference was found between the two groups in terms of mechanical ventilation need, intensive care admission rate, thrombosis and mortality. In terms of laboratory findings, those with positive aPLs have higher median C-reactive protein (CRP) and ferritin values than those with negative aPLs. In our study group, we could not find a relationship between aPLs positivity and critical complications. According to our hypothesis, it may not be necessary to routinely examine aPLs in patients with a diagnosis of COVID-19 to determine the risk of thromboembolic complications.

Prothrombotic role of antiphospholipid antibodies in a patient with sickle cell disease

&lt;abstract&gt; &lt;p&gt;Sickle cell disease (SCD) is a common inherited condition in African, Caribbean, and Mediterranean countries. SCD is a hematologic disorder caused by a well-characterized point mutation in the β-globin gene, which produces an abnormal hemoglobin S that results in the sickling of red blood cells in deoxygenated conditions. Patients with SCD display a “hypercoagulation state” leading to an increased risk of severe venous and arterial thrombotic vascular events. Herein we report a case of severe thrombotic complications in a patient with SCD who showed high antiphospholipid antibodies (APA) levels during vascular occlusions.&lt;/p&gt; &lt;/abstract&gt;

Ispitivanje povezanosti između vrste i titra antifosfolipidnih antitela sa kliničkim manifestacijama antifosfolipidnog sindroma

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by arterial or venous thromboses and/or spontaneous abortions associated with a persistently elevated level of antiphospholipid antibodies. To date, no clear relationship has been established between levels and types of autoimmune antibodies and clinical manifestations of APS, which can range from mild coagulation disorders to life-threatening conditions. Aim: The aim of this study is to examine the relation between antiphospholipid antibody type and titer and the most common clinical manifestations of APS. Materials and methods: The retrospective study included 32 patients with a confirmed laboratory finding of elevated antiphospholipid antibodies, who came for follow-up examinations to the Hemophilia Unit of the University Clinical Center of Serbia, between June 1, 2017 and December 31, 2018. Data on patients were taken from their medical records. Basic demographic data, type and titer of antiphospholipid antibodies, and their association with the present clinical manifestations of APS were analyzed using standard statistical methods. Results: There was no significant difference regarding the frequency of positive results for lupus anticoagulant, anti-cardiolipin, and anti-beta-2-GP-I antibodies, between the symptomatic and asymptomatic group. The percentage of persons with simultaneous positivity for two or all three antiphospholipid antibodies was the same in both groups of subjects. Conclusion: As opposed to previous studies, our study did not demonstrate a correlation between the titer of antiphospholipid antibodies and the clinical manifestations of APS. Symptomatic and asymptomatic patients did not significantly differ in the frequency of elevated antibodies. These results indicate that the presence of other factors, which are as yet little-known, is necessary for the clinical manifestations of APS.

Antiphospholipid antibodies and their role in the development of placental dysfunction

The objectives: to assess the spectrum and diagnostic value of antiphospholipid antibodies (APLA) by placental dysfunction. Materials and methods. A study of the APLA spectrum in 122 patients with placental dysfunction in the II and III trimesters of pregnancy was carried out. The control group included 64 practically healthy women in the II and III trimesters of pregnancy with a physiological course of gestation and without a complicated reproductive and somatic history. Results. The overall frequency of detection of critical APLA in the group of women with placental dysfunction was 46.7%, while in women with a physiological course of pregnancy there were no cases of a positive serological reaction to the content of APLA. The number of patients with high and medium titers of IgG and IgM (critical APLA) was low – 11.5%. Noncritical APLA (antiphosphatidylethanolamine and antiphosphatidylserine IgM and IgG antibodies) were more often determined in low and medium titers in patients with placental dysfunction without pronounced hemodynamic changes and were detected in 36.9% of cases.Most of the patients with circulating antibodies to cardiolipin and β2-glycoprotein-1 (21 (17.2%) people) had low (up to 20 U/ml) levels of APLA. The median APLA level in patients with placenta-associated complications which were associated with placental dysfunction (28.5 (18.1) was higher than in patients without these complications (18.6 (7.4); P&lt;0.01).Conclusions. The circulation of APLA in the mother’s blood is of a great importance for predicting of the placental dysfunction development and its severity. An increase concentration of circulating APLA in the maternal blood serum correlates with the frequency of severe forms, the timing of the onset of placental dysfunction and the development of placenta-associated pregnancy complications. In placental dysfunction, the APLA spectrum includes lupus anticoagulant, antibodies to cardiolipin, phosphatidylserine and phosphatidylethanolamin. Their identification increases the efficiency of diagnostics of antiphospholipid syndrome.

Вплив антифосфоліпідних антитіл на ризик невдалої імплантації після запліднення in vitro

Infertility is a unique pathology because it concerns a couple, not one person, and is the cause of a whole range of medical, social, demographic and economic problems. With the active development of assisted reproductive technologies, the demand for solving the problem of infertility has grown significantly. However, the prevalence of infertility remains stable, indicating many «white» spots in the diagnosis and treatment of this pathology and determining the search for new risk factors, diagnostic criteria, and treatment algorithms. Purpose — to analyze the factors that may affect implantation, namely the presence of lupus anticoagulant and antiphospholipid antibodies in women with infertility who have undergone in vitro fertilization. Materials and methods. A survey of 106 women diagnosed with infertility underwent treatment with assisted reproductive technologies in September 2019 — February 2021. The control (1) group consisted of women who received infertility treatment according to the standard scheme: controlled ovarian stimulation, gamete collection, intracytoplasmic sperm injection and embryo transfer. The main (2) group included patients who received aspirin, anticoagulants, and intravenous IgG immunoglobulins in addition to the standard treatment regimen. In the present study, levels of lupus anticoagulant and antiphospholipid antibodies were determined in both groups. Results. The study found no differences between groups of patients in levels of antibodies (AB) to phospholipids (IgG), beta-2-glycoprotein (IgG, IgM) and lupus anticoagulant (screening, confirmation) in the two groups of patients (p&gt;0.05). Difference in two groups were in levels of AB to beta-2-glycoprotein IgM in controls, on average, 9.42 units/ml (5.86 units/ml — 12.35 units/ml), and in patients of main group — 7.23 units/ml (3.14 units/ml — 10.58 units/ml), p=0.015. One-factor logistic regression models were used to clinically understand the influence of factors associated with the risk of implantation failure. The analysis did not reveal a connection between risk of implantation failure and levels of autoantibodies (aAB) to phospholipids (IgG, IgM), beta-2-glycoprotein (IgG, IgM) and lupus anticoagulant (screening, confirmation) in two groups of patients (p&gt;0.05 in all cases). Conclusions. The presence of aAB and/or antiphospholipid syndrome during the establishment of infertility factors is an essential component of the algorithm for diagnostic search for the cause of infertility and miscarriage. However, based on the obtained data, the presence of aAB in the study does not affect the implantation process nor affects the treatment of infertility. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: infertility, implantation failure, antiphospholipid syndrome, assisted reproductive technologies.

A SYSTEMATIC LITERATURE REVIEW OF BUDD-CHIARI SYNDROME IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Antiphospholipid syndrome is associated with multiple and recurrent episodes of arterial and venous thrombosis, thrombocytopenia, spontaneous fetal losses, and high levels of antiphospholipid antibodies. These antibodies can also be present in systemic lupus erythematosus (SLE), and predispose patients with Lupus to a hypercoagulable state. Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow obstruction that can lead to hepatic congestion and it is deeply associated with acquired or inherited hypercoagulable states. Therefore, the aim of this study was to conduct a systematic literature review to analyze the association between Budd-Chiari syndrome and SLE. A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Articles were selected from PubMed/Medline, SciELO and LILACS databases in August 2021 using the search terms [Lupus] OR [SLE] AND [Budd-Chiari syndrome]. The inclusion criterion was limited to observational studies, case reports or case series that reported an association between Budd-Chiari syndrome and SLE. Language was restricted to English, Spanish or Portuguese. Among 76 articles initially identified, 31 were eligible for this review after full texts were read. The vast majority of the studies have linked the antibodies lupus anticoagulant and anticardiolipin as etiological factors of BCS in patients with lupus. One study has reported six cases in which factor V Leiden was strongly related to SLE, suggesting that this mutation should also be investigated in patients with lupus and BCS. Few studies have mentioned isolated deficiency of protein C and/or protein S as common etiologies of BCS in patients with lupus. Studies suggest that Lupus anticoagulant can be sought in patients with idiopathic hepatic venous thrombosis. Possible mechanisms by which antiphospholipid antibodies induce thrombotic events in patients with SLE have been suggested: it can bind to platelet membrane phospholipids and accentuate their adhesion and aggregation ability, it can interfere in the interactions of proteins C and S and impair the formation of the coagulation control complex (activated protein C, protein S and factor V). Budd-Chiari syndrome can be a rare complication in patients with SLE. A methodical search for hepatic vein occlusion in patients with SLE who develop unexplained hepatomegaly should be performed. In addition, screening for lupus anticoagulant and anticardiolipin antibodies should take place to reduce the percentage of apparently idiopathic BCS cases.

The relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients

Objective: Assess the relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients. Methods: Case control study. A total of 385 patients (149 males and 236 females, aged from 1 to 105 years, with a median age of 37 years) who were hospitalized in Peking University First Hospital from January 2015 to December 2019 and tested positive for any one of the anti-phospholipid antibodies were included in the study. All subjects were divided into thrombotic group and non-thrombotic group according to whether thrombus was detected by imaging examination during hospitalization. In thrombosis group, there were 66 males and 36 females, aged from 3 to 105 years, with a median age of 58 years. In non-thrombosis group, there were 83 males and 200 females, aged from 1 to 94 years, with a median age of 31 years. Clinical data and laboratory data of patients were recorded. ACL-IgM/IgG and anti-β2GPI-IgM/IgG were detected by ELISA and LA was detected by dRVVT and SCT on automatic coagulation analyzer. The rates of age, gender, smoking, obesity, hypertension, hyperlipidemia, diabetes and the median level of antiphospholipid antibodies were compared between two groups. Logistic multivariate regression analysis was used to determine the risk factors for thrombotic events. The mid-to-high titer value of aCL was established by the χ2-trend test and verified by logistic regression. Results: The median age (58 years) and the rates of male (64.7%), smoking (16.7%), hypertension (63.7%) and diabetes (28.4%) in thrombus group were significantly higher than those in non-thrombus group (Z=7.685, χ²=38.077, 16.312, 37.769, 24.749 respectively; P<0.01). The positive rate of anti-β2GPI-IgG and dRVVT in thrombosis group (11.8% and 78.4%) was significantly higher than that in non-thrombosis group (5.3% and 60.1%), as well as the median level of dRVVT (1.29 RU/ml vs 1.23 RU/ml) (χ²=3.864 and 10.309, Z=3.539; P<0.05). The median level of aCL-IgM was higher in non-thrombosis group (2.3 MPL vs 2.0 MPL). The positive rate of aCL-IgG was slightly higher in thrombosis group (18.6% vs 10.6%). Logistic regression analysis showed that men, hypertension, diabetes, advanced age, elevated dRVVT, and elevated anti-β2GPI-IgG are risk factors for thrombosis. Taking 36 GPL as the medium-to-high titer value of aCL-IgG, the risk of thrombosis increased by 2.45 times. Conclusions: In the anti-phospholipid antibody profile, LA detected by dRVVT method, anti-β2GPI-IgG and aCL-IgG may be valuable laboratory indicators for inpatient thrombotic events. The mid-to-high titer value of aCL-IgG is set at 36 GPL to distinguish the risk of thrombosis.

Altered platelet and coagulation function in moderate-to-severe COVID-19

To reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about ¼ of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro. Contraction of blood clots was hindered in about ½ of patients, especially in severe and fatal cases, and correlated directly with prothrombotic parameters. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompacted intravital clots are more obstructive but patients could also be prone to bleeding. The absence of consumption coagulopathy suggests the predominance of local and/or regional microthrombosis rather than disseminated intravascular coagulation. The results obtained (i) confirm the importance of hemostatic disorders in COVID-19 and their relation to systemic inflammation; (ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction; (iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.

Features of laboratory markers in pregnant women with antiphospholipid syndrome and retrochorial hematoma

The aim. Study of hemostasis, antiphospholipid antibody levels and immunological parameters in pregnant women with antiphospholipid syndrome (APS), in particular with retrochorial hematoma (RCH).&#x0D; Materials and methods. 90 women were selected and divided into two groups: the control group – 30 pregnant women with a normal pregnancy (without APS) and the main group – 60 pregnant women with APS. Women in the main group were diagnosed with APS before pregnancy. In turn, the main group was divided into two subgroups: 1 subgroup – 41 pregnant women without RCH and 2 subgroup – 19 pregnant women with RCH.&#x0D; The main indicators of hemostasis were determined in all pregnant women, namely: the degree and rate of platelet aggregation, Willebrand factor, D-dimers. In addition, the level of antiphospholipid antibodies (APLA), antibodies to β2-glycoprotein, to annexin V, to prothrombin was examined, and the level of annexin V was also determined. The absolute and relative content of Treg, CD3+, T-lymphocytes, CD4+ (T-helpers), CD8+ (cytotoxic T-lymphocytes), CD19+ (B-lymphocytes), CD16+CD56+ (NK cells), CD16+CD56+CD107a+ (activated NK cells).&#x0D; Results. The obtained results showed that in pregnant women with APS compared to pregnant women without APS there are statistically significantly higher values of the degree and rate of platelet aggregation (90.6±6.3% and 106.3±6.7% vs. 65.3±5.3 % and 73.4±5.6%, respectively). There were also higher values ​​of Willebrand factor and D-dimers (2.5±0.3 IU/ml and 378.1±34.3 ng/ml against 1.7±0.2 IU/ml and 268.1±27, 3 ng/ml, respectively).&#x0D; APLAs were significantly higher in pregnant women with APS compared with pregnant women in the control group, namely: 16.1±1.5 vs. 3.8±0.4 U/ml. With regard to antibodies to β2-glycoprotein, to annexin V, to prothrombin and to the level of annexin V, their values were also statistically significantly higher in the group of pregnant women with APS.&#x0D; In addition, the results of the study showed that pregnant women with APS showed changes in subpopulations of immunocompetent cells.&#x0D; However, examining the difference in hemostasis, antibody content, and level of lymphocyte subpopulations between pregnant women with APS with and without RCH, it was found that their shifts in pregnant women with RCH were more pronounced than in women without RCH.&#x0D; Conclusions. Pregnant women with APS are characterized by significantly more significant changes in hemostasis, manifested by activation of intravascular thrombosis. In addition, such pregnant women had a significantly higher concentration of autoantibodies. There are also changes in the immune system, in particular, a decrease in Treg-cells, which have the ability to reduce the specific proliferation and effector functions of lymphocytes, thereby participating in the pathogenesis of APS.

Coronavirus-disease-2019-induced antiphospholipid-like syndrome: a case report

BackgroundThis paper describes a case of antiphospholipid syndrome-like condition caused by coronavirus disease 2019. The medical community still faces many diagnostic and therapeutic challenges vis-à-vis coronavirus disease 2019. Ultimately, coronavirus disease 2019 is diagnosed on the basis of laboratory and radiological findings. Considering the high rate of mortality due to coagulation abnormalities and thrombosis among coronavirus disease 2019 patients, it is important to pay attention to the differential diagnoses of coronavirus disease 2019 and other diseases following thrombotic events.Case descriptionThe patient was a 56-year-old Iranian man who underwent coronary artery bypass graft surgery and mitral valve repair. During hospitalization, the patient showed an elevated level of anticardiolipin antibody (immunoglobulin G isotype), antiphospholipid antibodies, and thrombosis in the brachial artery of the left hand, based on which a differential diagnosis of antiphospholipid syndrome was made. However, ultimately, the coronavirus disease 2019 polymerase chain reaction test and computed tomography scan of the lungs showed that the patient had coronavirus disease 2019.ConclusionAccording to the few studies performed on coronavirus disease 2019 patients, elevated levels of the isotypes of antiphospholipid antibodies in coronavirus disease 2019 patients create conditions similar to antiphospholipid syndrome, which, in the absence of reliable coronavirus disease 2019 testing, can lead to misdiagnosis and consequently delayed or improper treatment. Therefore, to provide timely and appropriate treatment, it is important to pay attention to differential diagnosis.

Вакцина Гам-КОВИД-Вак (Спутник V) не оказывает негативного влияния на сперматогенез у мужчин

Relevance. During the pandemic and large-scale vaccination against COVID-19, studies of the effect of various types of vaccines on human reproductive function have become particularly important. Vaccination may have a negative impact on the reproductive organs and tissues due to the development of an autoimmune process involving the gonads. Currently, there are some studies on the effect of vaccination against coronavirus infection caused by SARS-CoV2 on the male and female reproductive function. The absence of a negative effect of vaccination on spermatogenesis in men has already been demonstrated in the results of three studies. Objective. To evaluate the effect of the Gam-COVID-Vac (Sputnik V) vaccine on spermatogenesis and the level of antiphospholipid antibodies in men. Materials and methods. The prospective study included 45 men who were vaccinated against COVID-19 with Gam-COVID-Vac (Sputnik V). The criteria for inclusion in the study were the age from 18 to 55 years, the absence of a previous history of COVID-19, a negative RT-PCR result in SARS-CoV-2 testing, negative SARS-CoV-2 IgG results prior to vaccination, and the absence of severe somatic diseases. The patients were examined twice: immediately before vaccination and 90 days after the first dose was injected. We evaluated spermogram parameters, determined the levels of FSH, LH, TSH and total testosterone, and analyzed blood for IgM and IgG antiphospholipid antibodies (aPL) to cardiolipin (aCL), β2-glycoprotein-1 (as2-GP1), annexin V (aAnV), phosphatidylserine (aPS), as well as IgG antibodies to SARS-CoV-2 using enzyme immunoassay. Results. There were no significant changes in the parameters of spermogram and hormone levels before and after vaccination;men with moderate impairment of spermatogenesis (oligoasteno-and/or teratozoospermia) did not show considerable changes either. The level of aPL after vaccination did not increase compared to the baseline level. Besides, there was no correlation between the dynamics of the level of antisperm antibodies, aPL and spermogram parameters. These findings indirectly indicate that there are no changes in the reproductive function associated with this autoimmune factor after vaccination in men. Conclusion. This is one of the first studies that has revealed the effect of the Gam-COVID-Vac vaccine on spermatogenesis, hormonal profile and aPL level in men. The obtained results demonstrate that the Gam-COVID-Vac vaccine does not have a negative effect on the reproductive function in men.

Вакцина Гам-КОВИД-Вак (Спутник V) не оказывает негативного влияния на овариальный резерв у женщин репродуктивного возраста

Relevance. There is limited evidence on the effect of various vaccines on the human reproductive system. Potential adverse effects of vaccines on fertility are associated with autoimmune disorders, which might cause gonadal damage. Currently, several studies are underway investigating the impact of COVID-19 vaccines on human fertility. To our best knowledge, there is only one study published which demonstrated no adverse effects of the COVID-19 vaccine on assisted reproductive technology outcomes. Aim. To investigate the effect of the Gam-COVID-Vac (Sputnik V) vaccine on ovarian reserve and antiphospholipid antibody level in reproductive-age women. Materials and methods. The prospective study included 51 women vaccinated against COVID-19 with Gam-COVID-Vac (Sputnik V) vaccine. The inclusion criteria were age from 18 to 45, preserved menstrual function, normal ovarian reserve, no history of COVID-19, negative PCR test result for SARS-CoV-2 and negative SARS-CoV-2 IgG antibody test before vaccination, no pregnancy, and no history of serious illnesses. Clinical evaluation was carried out twice-immediately before immunization and 90 days after the first vaccine component administration. The antral follicle count was measured by pelvic ultrasound. Serum levels of AMH, FSH, TSH, estradiol, antiphospholipid antibodies (aPL) M and G isotypes against cardiolipin (aCL), β2-glycoprotein-1 (aβ2-GP-1), annexin V (aAn V), phosphatidylserine (aPS), and IgG antibodies against SARS-CoV-2 were measured by enzyme immunoassay. Results. There were no significant changes in hormones levels and antral follicle counts before and after vaccination, including in women of advanced reproductive age (≥37 years). After immunization, aPL antibody levels did not differ significantly from the baseline. There was no correlation between aPL antibody level dynamics and level of FSH and AMH, which indirectly demonstrates no possible autoimmune effect of vaccination on women's fertility. Conclusion. This is the first study investigating the effect of the Gam-COVID-Vac vaccine on ovarian reserve parameters and aPL antibody levels. The preliminary results prove that the Gam-COVID-Vac vaccine in women of reproductive age does not adversely impact ovarian reserve.

An Exploration of the Reproductive Health Concerns in Women with Systemic Lupus Erythematosus

An Exploration of the Reproductive Health Concerns in Women with Systemic Lupus Erythematosus

MiR-19b-3p and miR-20a-5p are associated with the levels of antiphospholipid antibodies in patients with antiphospholipid syndrome

Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-β2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.

Antiphospholipid antibodies levels and potential effects on in-vitro fertilization in a large cohort of infertile Syrian women

BackgroundObstetric morbidities represent a common hallmark manifestation of antiphospholipid syndrome (APS), with the recurrent loss of pregnancy as the main complication. The presence of antiphospholipid antibodies (APA) and its potential impact have not been established yet in infertile women seeking assisted reproduction technologies in Syria.This study aims to determine the prevalence of anticardiolipin antibodies (aCL) and lupus anticoagulation (LAC) and their association with age and the In vitro fertilization (IVF) outcomes in a large sample of Syrian women. Materials and methodsThe electronic patients’ records were screened and relevant data extraction was performed retrospectively. The study included 876 women who had IVF between January 2012 and January 2020 in a tertiary care hospital. ResultsThe prevalence of APA among the included women was less than 1%. Only 5 patients had positive APA. No correlation was found between the APA levels and age. Additionally, the APA did not have an impact on neither the IVF outcomes nor the number of IVF cycles. Conclusionthe added value of APS antibodies’ screening could be considered very modest when compared to its financial burden on patients since it has a very low prevalence in women having IVF.

Evaluation of risk factors and biomarkers related to arterial and venous thrombotic events in idiopathic inflammatory myopathies

Objectives: This study aimed to assess the contribution of traditional/disease-related risk factors and biomarkers linked to arterial and venous thrombotic events (TEs) in patients with idiopathic inflammatory myopathies (IIMs). Method: The occurrence of arterial and/or venous TEs at the time of or after IIM diagnosis was retrospectively evaluated in a cohort of 253 patients with IIMs, resulting in a final population of 246 IIM patients, 51 with reported TE (cases) and 195 without a history of TE (comparators). Information on disease characteristics and traditional risk factors for arterial and venous TE (essential hypertension, diabetes, dyslipidaemia, smoking, malignancy) was retrieved. Serum levels of anti-phospholipid antibodies (aPLs) and adhesion molecules were analysed at the time of IIM diagnosis and at the time of the TE in cases. Results: One in five IIM patients (21%) had experienced a TE, arterial TE in 22 and venous TE in 29 patients, with a peak prevalence within 5 years after diagnosis. Among traditional/disease-related risk factors, only older age was associated with both arterial and venous TEs, after adjusting for other covariates. Low serum levels of e-selectin were associated with higher odds of developing a TE, without specific association with either arterial or venous TEs. Only 6% of IIM patients had aPLs, with no significant difference between cases and comparators. Conclusions: An increased risk of both venous and arterial TEs should be considered in IIM patients, particularly close to diagnosis and in elderly people. Low serum levels of e-selectin may predict TE in IIM patients, but the underlying biological mechanism is not known.

Risks of reproductive loss and placenta-mediated pregnancy complications in women with antiphospholipid antibodies

Introduction. Antiphospholipid syndrome (AРS) is a multisystem disease characterized by elevated levels of antiphospholipid antibodies (AРA), arterial and/or venous thrombosis, thrombocytopenia, and habitual miscarriage. Various AРA types have multifactorial and indirect effects on pregnancy course from the earliest stages, leading to termination of pregnancy and putting the prerequisites for further obstetric complications. Aim: determine rate and relative risk of pregnancy complications in AРA carriers. Materials and Methods. The retrospective study, conducted between 2017 and 2019, included 268 pregnant women. All women underwent a comprehensive study consisting of clinical examination and laboratory methods. AРA of IgM and IgG classes were measured by using ELISA, lupus anticoagulant (LA) was estimated by using a coagulometer. Results. APA were detected in 213 (79.48 %) women examined; 55 (20.52 %) patients (n = 55) lacked APA. Failed in vitro fertilization attempts were 2 times more common in women with AРA (10.33 vs. 5.45 %, respectively; p &lt; 0.001). Also, significant differences were found in this group in antenatal fetal death (4.23 vs. 1.82 %, respectively; p &lt; 0.001) and chronic placental insufficiency without fetal malnutrition (23.47 vs. 18.18 %, respectively; p &lt; 0.05). Of 165 women with early pregnancy loss syndrome, AРA were found in 130 (78.79 %), late pregnancy loss – in 29 (76.32 %) and antenatal fetal death – in 9 (90.0 %) women carrying serum AРA. The relative risks of unfavorable pregnancy outcomes have been identified for various AРA subtypes. Conclusion. Identifying clear-cut relative risks of adverse pregnancy outcomes for various subtypes of antiphospholipid antibodies will allow to determine risk groups and develop a special treatment algorithm for preventing pregnancy complications and perinatal losses.