Levels Of Anticardiolipin Antibodies Research Articles

#1707 Antiphospholipid antibodies in lupus nephritis

Abstract Background and Aims Antiphospholipid antibodies (aPL) constitute a heterogeneous family of antibodies against anionic phospholipids or phospholipid-binding proteins. They may occur in association with autoimmune diseases, infections, and sometimes in the general population. Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). The aim of this study was to investigate the association of aPL with clinical activity, renal damage, renal activity and outcomes in patients with LN. Method A total of 157 patients (11 male, 146 female, age between 17 and 58 years) with LN were included in this study. The International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification of LN was used to classify the patients into LN subsets. Histopathological renal activity and damage were estimated using the Activity Index (AI) and Chronicity Index (CI), respectively. Levels of anticardiolipin (aCL) antibodies, anti-β2-glycoprotein I (anti-β2-GPI) antibodies and lupus anticoagulant (LAC) were measured, and other clinical and pathological data were also obtained. Long-term renal outcome was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease stage, after a median follow-up of 20,5 ± 8, 7 years, counting from the occasion of the first renal biopsy. Renal and extra-renal symptoms were analyzed. Patients which have more than one class LN features, were excluded from the study. The treatment includes standard treatment for LN, inhibitors of the angiotensin system in patients with hypertension and proteinuria, steroids, anticoagulants, cyclophosphamide, mycophenolate mofetil, azathioprine. Results LN patients were classified according to the baseline renal biopsies as patients with: minimal mesangial LN (4), mesangial-proliferative LN (30), focal proliferative LN (31), diffuse proliferative LN (48), membranous LN (44). aPL antibodies were detected in 89 (56,69%) patients, aCL antibodies – in 72 (45,86%), anti-β2-GPI antibodies – in 58 (36,94%) and LAC were detected in 46 (29,30%) patients. None of these patients had a concomitant diagnosis of antiphospholipid syndrome nephropathy. Follow-up was similar between aPL-positive and aPL-negative patients. LN patients with positive aPL antibodies had significantly higher SLEDAI (p < 0,05), anti-dsDNA levels (p < 0,05), anti-ribosomal-P antibodies levels (p < 0,05), anti-C1q antibodies (p < 0,05), lower serum C3 (p < 0,005) and C4 (p < 0,05) levels, and higher intensity of complement C3 (p < 0,05) deposits in kidney tissue than the aCL antibody–negative LN patients. aPL-seropositivity was associated with more rapid decline in eGFR (–1,06 mL/min/year compared to –0,45 mL/min/year in aPL-seronegative patients) and showed inferior patient survival (89,8% and 67,9% at 10 and 15 years, respectively, compared to 97,3% and 76% in aPL-seronegative patients). No significant correlation was found between serum aPL antibodies levels and activity or chronicity index scores in renal biopsies at baseline, ANA levels, or age. Conclusion We concluded that aPL-seropositivity are correlated with clinical activity in patients with LN and are associated with inferior long-term patient survival.

E030 Osteonecrosis of the spine in antiphospholipid antibody syndrome

Abstract Background/Aims Osteonecrosis (ON) is a well-known complication of several rheumatic diseases, affecting the hip, knee, shoulder, or ankle. The involvement of spine and other sites with ON has been reported with catastrophic APS, although the nature of this association is not completely clear. In antiphospholipid syndrome, thrombosis of blood vessels is considered a possible mechanism, along with other risk factors, such as active disease, thrombocytopenia, glucocorticoid use and associated autoimmune diseases, making the pathophysiology multifactorial. We report a case of a 66-year-old male with APS who developed bone infarcts/osteonecrosis after withdrawal of anticoagulation for APS, which was necessitated by a bleeding complication and introduction of steroids for immune thrombocytopenia. Methods A 66-year-old male came to us with history of unprovoked deep vein thrombosis (DVT) for which he was on antiplatelet and anticoagulation for over 20 years. He was diagnosed to have high titre anti cardiolipin antibody (ACA)(186 U/ml) without other autoimmune conditions. He had an episode of bladder hematoma in August 2022, needing his anticoagulation to be suspended temporarily. He was also found to have profound thrombocytopenia with raised inflammatory markers. Considering it to be immune mediated he was started on high dose oral corticosteroids and was later maintained with azathioprine while the oral prednisolone dose was gradually brought down to 10 mg daily in about 3 months’ time. His thrombocytopenia improved progressively however he developed an unprovoked DVT in October 2022 and was restarted on anticoagulation. He continued to have low dose steroids for about 6 months. Meanwhile, he started having a new onset of low back pain in December 2022. An MRI of the whole spine showed multilevel osteonecrosis with haemorrhagic cavities in a few vertebral bodies. Results This case highlights three interesting points. The first is the atypical presentation of the osteonecrosis involving vertebral bodies. Osteonecrotic lesions in the spine of a patient with catastrophic primary antiphospholipid syndrome has been reported. Our case signifies that although vertebral bodies are an uncommon site for avascular necrosis in patients with APS, it is not rare. Secondly, the pathogenesis of ON is complex. Whether ACA are directly responsible for this condition or whether they are the bystanders remains controversial. ACA have shown to be an independent risk factor for developing ON in many studies. Thirdly, steroids are known to be an important risk factor in patients presenting with osteonecrosis. The vascular compromise could be attributed to a steroid induced hypercoagulative state, abnormal lipid metabolism, or fat embolism. Conclusion ON in APS is unusual and its underlying pathophysiology remains multifactorial. However, when complicated by the high ACA levels, active disease, difficult anticoagulation (bleeding tendencies), thrombocytopenia or prolonged use of steroids, it can lead to hypercoagulable state causing micro thrombosis and avascularisation. Disclosure M. Shah: None. K. Putchakayala: None.

Major low-energy trauma results in non-specific immunoglobulin generation without evidence for specific autoantibody production: A prospective cohort study.

Cellular debris resulting from large trauma might overwhelm the scavenger mechanisms and lead to autoimmune reactions. We analysed whether a major well-defined trauma in humans induces laboratory signs of transient autoimmunity in the months after the insult. We included 50 patients with pertrochanteric femur fracture undergoing intramedullary nail osteosynthesis in a prospective cohort study and followed them at 3-4 days, 6 weeks, 12 weeks and 12 months postoperatively. By standard techniques, we assessed levels of total immunoglobulins, anti-nuclear antibodies (ANA), anti-cardiolipin antibodies, anti-dsDNA antibodies and anti-C1q antibodies, as well as antibodies against cytomegalovirus (CMV) as a control. Blood leukocyte differential and lymphocyte subpopulations were determined at baseline and in the first two postoperative samples. The mean age of the patients reached 80.1 years, and 23 (46%) completed all visits. Serum concentrations of total IgG, IgM and IgA increased at all follow-up time points. The ANA fluorescence light intensity units increased at 12 weeks and 12 months postoperatively (p < 0.0001), but the proportion of ANA-positive patients did not change (35%). The values of anti-C1q mildly increased at all follow-up visits, but not the ratio to total IgG. Anti-dsDNA remained negative in all patients, and anti-cardiolipin IgG/IgM antibodies did not change. Anti-CMV IgG antibodies increased significantly at all follow-up visits, without change in the ratio to total IgG. Flow cytometry showed an increased proportion of B-cells 3-4 days postoperatively. In conclusion, major musculoskeletal trauma in elderly patients induces a generalized non-specific increase in immunoglobulin production without laboratory signs for enhanced systemic autoimmunity.

The Influence of Hyperthyroidism on the Coagulation and on the Risk of Thrombosis.

Introduction: Apart from the well-known fact that hyperthyroidism induces multiple prothrombotic disorders, there is no consensus in clinical practice as to the impact of hyperthyroidism on the risk of thrombosis. The aim of this study was to examine the various hemostatic and immunologic parameters in patients with hyperthyroidism. Methods: Our study consists of a total of 200 patients comprised of 64 hyperthyroid patients, 68 hypothyroid patients, and 68 euthyroid controls. Patient thyroid status was determined with standard tests. Detailed hemostatic parameters and cardiolipin antibodies of each patient were determined. Results: The values of factor VIII (FVIII), the Von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and anticardiolipin antibodies of the IgM class were significantly higher in the hyperthyroid patients than in the hypothyroid patients and euthyroid controls. The rate of thromboembolic manifestations was much higher in hyperthyroid patients (6.25%) than in hypo-thyroid patients (2.9%) and euthyroid controls (1.4%). Among hyperthyroid patients with an FVIII value of ≥1.50 U/mL, thrombosis was recorded in 8.3%, while in hyperthyroid patients with FVIII value ≤ 1.50 U/mL the occurrence of thrombosis was not recorded. The incidence of atrial fibrillation (AF) was significantly higher (8.3%) in the hyperthyroid patients compared to the hypothyroid patients (1.5%) and euthyroid controls (0%). Conclusions: High levels of FVIII, vWF, fibrinogen, PAI-1, and anticardiolipin antibodies along with other hemostatic factors contribute to the presence of a hypercoaguable state in patients with hyperthyroidism. The risk of occurrence of thrombotic complications is especially pronounced in patients with a level of FVIII exceeding 150% and positive anticardiolipin antibodies of the IgM class. Patients with AF are at particularly high risk of thrombotic complications due to a hyperthyroid prothrombotic milieu.

Bilateral retinal hemorrhages after sequential endovascular treatment of bilateral unruptured cerebral aneurysms.

To report a case of bilateral retinal hemorrhages in a patient undergoing two separate endovascular interventions for bilateral cerebral aneurysms. A comprehensive ophthalmic examination was performed after the patient underwent each of two separate endovascular interventions for bilateral cerebral aneurysms. Multimodal imaging including widefield pseudocolor fundus photography, optical coherence tomography, and widefield fluorescein angiography (FA) was obtained. A systemic workup including genetic testing and hypercoagulability studies was performed. Dilated fundus examination revealed new visually significant ipsilateral retinal hemorrhages after each endovascular procedure. FA showed evidence of a peripheral retinal microangiopathy present in both eyes before the patient underwent her second endovascular procedure. Systemic workup revealed persistently elevated serum anticardiolipin IgM antibody levels at >99th percentile. Retinal complications after endovascular intracranial interventions are uncommon. This patient who developed bilateral retinal complications was found to have persistently elevated anticardiolipin antibody levels, a risk factor for thrombosis. Patients who develop retinal complications after endovascular intracranial intervention may benefit from systemic workup for hypercoagulable conditions.

A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures.

NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th-7th week of gestation-w.g.) and 66 women in the 11th-13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. A misbalance in the NKp46+NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46high cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46hightCD56++) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Our results showed that accentuated levels of NKp46+NK cells lead to a negative prognosis for early pregnancy courses in women.

Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study

Several antiphospholipid antibody (aPL) profiles (“triple” and lupus anticoagulant [LA] positivity) are associated with a higher risk for clinical manifestations of antiphospholipid syndrome (APS). Further risk is correlated with higher levels of anticardiolipin antibody (aCL) and anti-β2 glycoprotein-I antibody (aβ2GPI), and with aPL persistence. Given that the 3 aPL tests detect partially overlapping sets of antibodies, the primary goal of this study was to characterize the associations among aPL tests using AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) core laboratory data. The APS ACTION Registry includes annually followed adult patients with positive aPL based on the Revised Sapporo Classification Criteria. We analyzed baseline and prospective core laboratory data of the registry for associations among aPL tests using the Spearman rank correlation with Bonferroni-adjusted significance level for multiple comparisons. An aPL Load was calculated based on 6 tests (aCL IgG/IgM/IgA and aβ2GPI IgG/IgM/IgA); a receiver operating characteristic curve was used to evaluate the diagnostic performance of the aPL Load in predicting LA positivity. In 351 patients simultaneously tested for LA, aCL, and aβ2GPI, the frequency of moderate-to-high (≥40 U) titers of aCL and aβ2GPI IgG/IgM/IgA was higher in patients who were positive for LA vs those who were negative. An aPL Load was calculated for each patient to assess the overall aPL burden. For every 1-point increase in the aPL Load, the possibility of a positive LA test increased by 32% (odds ratio, 1.32; 95% CI, 1.2-1.5; P < .001). Based on core laboratory data from a large international registry, most aPL enzyme-linked immunosorbent assay ≥40 U and a high calculated aPL Load combining 6 aPL enzyme-linked immunosorbent assays were predictive of a positive LA. These data suggest that the combined quantitative burden of aPL may provide a mechanistic explanation of a positive LA.

A blinded multicenter investigation: Accentuated NK lymphocyte CD335 (NKp46) expression predicts reproductive failures after IVF.

The peripheral blood NK cell diversity is highly complex. Recent studies have described more than a thousand phenotypes sharing NK cell receptors (NKRs), across the leukocyte lineages. Previously, we have found that accentuated NK p46 phenotype has prognostic value for NK cytotoxicity status, and is characteristic for patients with recurrent implantation failure (RIF).In a blinded investigation we studied blood samples from IVF women before embryo transfer (pre-implantation genetic tested [PGT] embryos n = 116; not tested embryos n = 219). We studied NKp46 expression by flow cytometry and anti-cardiolipin antibody (aCL) levels. aCL results were transmitted to the clinic but NKp46 expression was blinded (for us and for the clinic) and not analyzed before termination of the study (end of last pregnancy). Association of NKp46 phenotype with clinical pregnancy rate (CPR), pregnancy failure (PF) rate and life birth rate (LBR) were analyzed. aCL positive and IvIg treated cases were excluded.IVF success was dependent on p46 NK phenotype in patients with PGT embryos. Elevated p46 expression on NK (>93%) as well as decreased (<66%) significantly reduce CPR (OR 12.7 and 3.8) without affecting pregnancy failure frequency. Both accentuations (taken together) resulted in a significant reduction of LBR (OR 3.9 p = 0.019) compared with non-accentuated phenotypes (p46 levels 66–93%). Elevated NK cell levels (>14.5% weakly) were associated with PF (OR 3.1 p = 0.069), but not significantly with reduced LBR. In contrast, numbers of NKCD335+ lymphocytes (>11.5%) were a significant predictor of PF (OR-4.0 p<0.05) and decreased LBR (OR 2.1 p = 0.06). At the same time, accentuated numbers of NKCD335neg lymphocytes (<0.7 and >4%) were also associated with decreased LBR (OR 2,65 p = 0.05). In patients with NKCD335++ numbers (<5 and >21%), we found a weakly association with IVF failure. We found similar associations in IVF patients without PGT -A but at lower significance levels regardless the higher number of patients. Impact of NKp46 phenotype for IVF success was significant in patients with donor's ET and almost imperceptible in patients > 35y.o. with own embryo transfer.Accentuated increased or decreased CD335 expression on NK was associated with embryo implantation failure. Balanced CD335 levels form a condition favorable for implantation. Elevated numbers of p46+NK (CD3-CD56+CD335+) predicts pregnancy failures at higher significance levels than elevated NK cell numbers. Elevated numbers of p46negNK (CD3-CD56+CD335-) indicate reduced LBR. Accentuation of p46 expression on NK cells is associated with reproductive failures. In combination with PGD it provides a powerful prediction algorithm and treatment option.

SAMD1 attenuates antiphospholipid syndrome-induced vascular injury and pregnancy complications.

ObjectiveThis study was intended to investigate the effect of SAMD1 on antiphospholipid syndrome (APS)‐induced vascular injury in human umbilical vein endothelial cells (HUVECs) and pregnancy complications in mice.MethodsThe expression of SAMD1 in APS patients and healthy controls was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Anti‐B2GPI and anticardiolipin antibody (ACA) levels were tested by enzyme‐linked immunosorbent assay, MMP‐9, iNOS, ICAM‐1, and MCP‐1 mRNA and protein levels determined by qRT‐PCR and Western blot, cellular senescence detected by β‐galactosidase staining, cell proliferation ability detected by CCK‐8 assay, cell viability detected by trypan blue staining, cell mobility detected by Transwell, and cell angiogenesis ability detected by matrigel tube formation assay. An APS pregnant mouse model was constructed, and the embryo absorption rate was calculated.ResultsSAMD1 expression was low in serum of APS patients, which was correlated with the history of thrombosis and the number of adverse pregnancies. Anti‐B2GPI and ACA levels were increased in APS. The expressions of MMP‐9, iNOS, ICAM‐1, and MCP‐1 were also significantly upregulated in HUVECs treated with APS serum. APS promoted HUVEC senescence and inhibited cell proliferation, migration, and angiogenesis. Overexpression of SAMD1 reversed the above results. Experiments on the APS pregnant mouse model confirmed that overexpression of SAMD1 reduced the rate of fetal loss.ConclusionSAMD1 may reduce APS‐induced vascular injury and embryo loss by regulating cellular senescence, proliferation, migration, and angiogenesis.

Anzi Mixture Reduces ACA Levels and Decreases the Embryo Absorption Rate of ACA Positive Abortion Mice via Modulating T-bet/GATA-3 Molecules and Th1/Th2 Cell-associated Cytokines

Background: Anti-cardiolipin antibody (ACA) positive abortion, as a category of immune abortion, is a refractory disease. Anzi mixture, a traditional Chinese medicine, could improve clinical symptoms of ACA positive abortion and modulate pregnancy hormone. Aims: To investigate the effects of Anzi mixture on serum cytokines in ACA positive abortion mice. Methods: β2-GPⅠcan bind to phospholipids on surface of cell membrane, resulting in a series of pathological reactions, such as ACA abortion, therefore, ACA positive abortion mouse model was established by administrating human β2-GPⅠ.Levels of ACA and embryo absorption rate of ACA abortion positive mice were evaluated. The cytokines, including IL-6, IL-2, IFN-γ, IL-4, and IL-10, were determined by ELISA. RT-PCR assay was used to detect gene transcription of T-bet and GATA-3 in PBMCs. Results : Embryo absorption rate in mice of Anti-Low group and aspirin group was significantly reduced compared with that in the abortion model mice (p&lt;0.05). Anzi mixture (Anzi-Low and Anzi-High group) remarkably decreased ACA levels in mice compared with those in Model group (p&lt;0.01). Anzi mixture (both Anzi-Low and Anzi-High group) markedly down-modulated IL-6 and IL-2 levels and up-modulated IL-10, IL-4, and IFN-γ levels compared with those of mice in Model group (p&lt;0.01). Anzi mixture significantly enhanced gene transcription of GATA3 and T-bet compared with those of mice in Model group (p&lt;0.01). Conclusions Anzi mixtures remarkably reduced ACA levels in peripheral blood of ACA positive abortion mice and decreased embryo absorption rate by modulating T-bet/GATA-3 signaling pathway and regulating Th1/Th2 cell-associated cytokines.

BushenHuoxue Recipe for the Treatment of Prethrombotic State of ACA-Positive Recurrent Miscarriage via the Regulation of the PI3K-AKT Signaling Pathway.

Background Although the Bushen Huoxue (BSHX) recipe is commonly used for the effective treatment of the prethrombotic state of recurrent abortions, its mechanism of action is unclear. In this article, we investigated the therapeutic effects of BSHX on anti-cardiolipin antibody (ACA) positive recurrent miscarriage mice and the molecular mechanism involved in the treatment of the prethrombotic state of ACA-positive recurrent miscarriages based on the PI3K-Akt signaling pathway, to provide a scientific basis for clinical practice. Methods An ACA-positive recurrent miscarriage mouse model and normal pregnancy mouse model were adopted in this experiment. Seventy CBA/J female mice were induced to establish the ACA-positive recurrent model; the mice were mated with DBA/2 male mice. Of these mice, 50 became pregnant, which were randomly divided into a BSHX high-dose group (BH, 2.52 g/kg), BSHX medium-dose group (BM, 1.26 g/kg), BSHX low-dose group (BL, 0.63 g/kg), model group (M, distilled water), and an aspirin enteric-coated tablet group; each group had 10 mice. In addition, 16 CBA/J female mice were induced to establish the normal pregnant mouse model; the mice were mated with BALB/C male mice. Of these mice, 10 became pregnant, which were used as the blank control group (C) and received distilled water by gavage. Stillbirth and abortion rates were recorded for each group, and the uterine tissue, urine, and serum were collected. The serum expression levels of ACA, interleukin-6 (IL-6), progesterone ,estradiol, and endometrial histological changes were compared between the groups. Metabolomics was performed on the urine and uterine tissues of both groups using UHPLC-QTOF/MS, and the expression levels of PI3K, p-PI3K, AKT, and p-AKT proteins in the uterine tissues were detected using Western blot. Results Compared with the model pregnancy group, the BSHX high-dose group, BSHX medium-dose group, and BSHX low-dose group all had a lower absorption rate of mouse embryos, improved uterine histopathological morphology, significantly reduced serum levels of ACA and IL-6, increased serum levels of progesterone and estradiol, and significantly upregulated uterine levels of p-AKT, PI3K, and p-PI3K proteins. The metabolomic results showed that the metabolic levels in the urine and uterine tissues were significantly altered in the mouse model of ACA-positive recurrent abortion. The results also suggested that the pathogenesis of ACA-positive recurrent abortion may be associated with metabolic pathways, such as pentose, glucuronide, lysine degradation, and steroid hormone biosynthesis. Conclusion The BSHX recipe improved the uterine histopathological morphology of pregnant mice and promoted vascular formation in uterine tissues. The mechanisms involved the reduction in serum ACA and IL-6 levels, the increment in serumprogesterone and estradiol levels, the upregulation of the levels of p-AKT, PI3K, and p-PI3K proteins, and the activation of the PI3K-Akt signaling pathway. These data will be useful for effective drug research and development.

Primary Antiphospholipid Syndrome with and Without Acute Myocardial Infarction/Angina: A Cross-Sectional Study.

IntroductionAcute myocardial infarct/angina (AMI-A) is a possible complication in primary antiphospholipid syndrome (pAPS) patients. This study compares data obtained from pAPS patients with and without AMI-A.MethodsThis cross-sectional study of 66 (85.2% female) pAPS patients (Sidney criteria). Demographics, clinical data, medication use, and antiphospholipid antibodies were evaluated. Patients were divided into two groups: pAPS with AMI-A and pAPS without AMI-A.ResultsSixty-six patients with primary APS (six with AMI-A and 60 without AMI-A) were selected. They were similar for demographics, disease duration, and anthropometrics (p > 0.05). Patients with AMI-A compared to those patients without AMI-A had more frequently dyslipidemia (66 vs. 28%, p = 0.05), systemic hypertension (83 vs. 37%, p = 0.02), and increased levels of lipoprotein (a) (116 ± 67 vs. 36 ± 35 mg/dl, p = 0.0002). Interesting, current physical activity (66.7 vs. 23%, p = 0.04) was more seen in the first group when compared to the second one. Patients with AMI-A used more statins (66 vs. 22%, p = 0.017) and acetylsalicylic (100 vs. 28%, p = 0.05). Higher median levels of IgM anticardiolipin antibodies [70 (0–120) vs. 9 (0–120), p = 0.03] were observed in the first group.ConclusionspAPS patients and AMI-A have distinct clinical and laboratory spectra from those without AMI-A. It is characterized by dyslipidemia and hypertension, hyper lipoprotein(a), and a lower IgM anticardiolipin frequency.

Bilateral isolated superior ophthalmic vein thrombosis: An initial presentation of antiphospholipid syndrome

<br>Bilateral superior ophthalmic vein thrombosis (SOVT) being extremely rare requires diligent evaluation for a definitive diagnosis. A 19-year-old male presented with pain and swelling around both eyes for 5 days. He had bilateral proptosis with gross limitation of movements (extraocular movement) and visual acuity of 6/9 in both eyes. On palpation, no mass was found. Contrast-enhanced magnetic resonance imaging orbit demonstrated bilateral superior ophthalmic vein dilation. Keeping a clinical suspicion of bilateral SOVT, systemic evaluation revealed raised anticardiolipin antibody levels at two occasions 12-weeks apart. A diagnosis of antiphospholipid syndrome was made and anticoagulant therapy was commenced. At 2-week follow-up, there was marked improvement in clinical features.<br>

Possible effect of the HLA-DQ2/DQ8 polymorphism on autoimmune parameters and lymphocyte subpopulation in recurrent pregnancy losses

Recurrent pregnancy loss (RPL) affects 1–2 % of women. Allo- and autoimmune disorders are a recognized factor for RPL and poor pregnancy outcomes. There is a link between antiphospholipid syndrome (APS), Hashimoto's thyroiditis or coeliac disease, and pregnancy losses. The prevalence of the HLA-DQ2/DQ8 polymorphism and genetic susceptibility to the development of celiac disease may be higher in women who experience RPL. A total of 95 women who had experienced two or more miscarriages were qualified into the study: 49 women with the HLA-DQ2/DQ8 polymorphism as the study group, and 46 as the control group. The prenatal test results of the women were evaluated, which revealed that the foetuses from the study group had higher nuchal translucency measurements than those of controls (1.85 mm vs 1.50 mm; p = 0.0024). A higher level of anticardiolipin antibodies (aCL) in the IgG class (18.38 GP L vs 11.37 GP L; p = 0.0039) and antithyroid peroxidase antibodies (aTPO) (87.67 IU/mL vs 11.87 IU/mL; p = 0.0062) was observed when compared to the control group. The presence of the HLA-DQ2.2 polymorphism was observed when higher nuchal translucency measurements and a higher aTPO concentration occurred. A relationship between the aTPO concentration and a higher birth weight of newborns was also shown. No significant differences between the groups were observed for peripheral blood lymphocyte subsets. A statistically significant relationship between the HLA-DQ2/DQ8 polymorphism and the increased concentrations of indicators of autoimmune disorders was indicated.

The Interaction of Sickle Cell Trait and Anticardiolipin Antibodies in Venousthromboembolism

IntroductionAmong the risk factors for venous thromboembolism (VTE) are inheritance of the sickle cell gene and antiphospholipid syndrome. Antiphospholipid antibodies are elevated in sickle cell disease but there is little information on its levels in sickle cell trait. The prevalence of anticardiolipin antibodies and association with VTE is equally not known in the Nigerian population.MethodsA case control study involving 50 consecutive patients with Doppler confirmed venous thromboembolism at the University College Hospital Ibadan and 50 apparently healthy individuals. Haemoglobin electrophoresis was carried out using cellulose acetate membrane. IgG and IgM anticardiolipin antibodies were assayed by ELISA.ResultsThe mean age of the patients was 58.7±18.5years, range of 21-89 years, there were 21 males (42%). Majority of the patients (42 (84%)) had deep venous thrombosis while five (10%) patients presented with pulmonary embolism, one had both deep venous thrombosis and pulmonary embolism. A patient had portal vein thrombosis and another, an intracardiac clot. Sedentary lifestyles, hypertension and concomitant malignancy were the most prevalent risk factors (34% each) (figure I). Both sedentary lifestyle and cancer were significantly associated with VTE (p<0.001). Sickle cell trait (Hb AS) occurred in the same number of patients and controls (eleven each). Higher levels of both IgG and IgM anticardiolipin antibodies were found among the VTE patients with sickle cell trait than controls. (Table 1) The mean levels of IgG antibody in Hb AS patients was 31.7 ± 12.8 GPL compared to 25 ± 13.8 GPL in the controls (p= 0.254) and mean IgM anticardiolipin antibodies in Hb AS patients was 18.7 ± 6.2 GPL while that of the controls was 16.8 ± 11.6 GPL (p= 0.633). The global mean levels of IgG and IgM anticardiolipin antibodies in the patients with VTE were 29.7 ± 9.1 GPL and 24.8 ±16.7 GPL respectively versus 28.5 ±13.7 GPL and 25.2 ±16.2 GPL in the controls. A multivariable logistic regression showed age, sedentary lifestyle and anemia as independent risk factors while a positive IgM anticardiolipin antibody appeared protective for VTE. (Table 2)ConclusionThe prevalence of sickle cell trait and anticardiolipin levels did not differ between VTE patients and healthy controls. Age, hypertension, sedentary lifestyle and malignancies were identified risk factors in our cohort of patients. Larger prospective studies may be helpful in determining the influence of sickle cell trait and antiphospholipid antibodies in venous thromboembolism. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pathogenetically justified tactics of management of pregnancy with retrochorial hematoma

Introduction. Retrochorial hematoma (RH) often detected during routine ultrasound examination represents one of the multiple causes resulting in early pregnancy loss. RH results from the detachment of the chorionic plate from the vertebrae of the uterine decidual membrane and may lead to complicated course of pregnancy.Aim: to develop a differential approach to diagnose and manage pregnancy with RH.Materials and Methods. A prospective open-ended interventional non-randomized study was conducted by enrolling 170 women. The main group consisted of 85 pregnant women with RH, which were divided into 2 groups: group I (n = 45) – patients with RH and burdened obstetric history; and group II (n = 40) – pregnant women with RH without a history of obstetric complications. The control group included 85 women with uncomplicated pregnancy. The incidence of hereditary thrombophilia was assessed by measuring rate of high thrombogenic risk mutations in the genes of factor (F) V Leiden and prothrombin (FII) G20210A; blood levels of lupus anticoagulant (LA) and anti-cardiolipin antibodies (aCL), β2-glycoprotein 1 (β2-GP1), annexin V and prothrombin; ADAMTS-13; rate of low thrombogenic risk polymorphisms, prevalence and spectrum of bacterial-viral infections.Results. It was revealed that women with RH had occasional genetic and acquired hemostasis defects as well as impaired florocenosis of the urogenital tract. Defects in the fibrinolysis system prevailed among the hereditary hemostasis defects: 75.5 % in group I, 32.2 % in group II, and 4.7 % in the control group. No decrease in the activity of natural anticoagulants – antithrombin and protein C was found. Among the acquired thrombophilic conditions, a large proportion of circulating antiphospholipid antibodies (APA) was found: 46.6 % in group I, 27.5 % in group II, and 2.3 % in the control group. Cervicitis of nonspecific etiology prevailed among dysbiosis signs: 53.3 % in group I, 47.5 % in group II and 11.7 % in the control group.Conclusion. RG formation is a multifactorial process, which pathogenesis involves both genetic and acquired factors such as APA, especially in combination with genetic thrombophilia (FV Leiden and FII G20210A), as well as inflammatory or pro-inflammatory status. We consider that all patients with RG as well as those with former RG are indicated to undergo the above-mentioned studies. It is advisable to include tranexamic acid, progesterone, low molecular weight heparins and antibiotics in the therapy regimen if indicated.

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.

Association of antiphospholipid antibodies with clinical activity and renal pathological activity in patients with lupus nephritis.

This study aimed to investigate the association of antiphospholipid antibodies (aPL) with clinical activity and renal pathological activity in patients with lupus nephritis (LN). Levels of anticardiolipin () antibodies, anti-β2-glycoprotein I (anti-β2-GPI) antibodies and lupus anticoagulant (LAC) were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. A total of 83 patients with LN were included in this study, 40 patients (48.2%) in the s positive group and 43 patients in the aPL negative group. LN patients with positive aPL had significantly higher SLEDAI (p = 0.012), more hematuria (p = 0.043), lower serum C3 (p = 0.003) and C4 (p = 0.014), and a higher pathological activity index (p = 0.012), more micro-thrombosis (p = 0.046) and more C3 deposits (p = 0.038) in the glomerulus than patients with negative aPL The level of IgG- was significantly correlated with SLEDAI and serum level of C3 (r = 0.44, p < 0.001; r = -0.39, p = 0.003, respectively). The level of IgM- was significantly correlated with SLEDAI, and serum levels of C3 and C4 (r = 0.27, p = 0.014; r = -0.22, p = 0.041; r = -0.23, p = 0.035, respectively). Our work suggests that aPL, especially, are correlated with both clinical activity and renal pathological activity in patients with LN.

Xenobiotics Targeting Cardiolipin Metabolism to Promote Thrombosis in Zebrafish.

Exposure to environmental pollutants is an important factor contributing to the development and severity of thrombosis. However, the important physiological molecules in the thrombotic processes affected by environmental exposures remain unknown. In this study, we show that exposure to environmental chemicals disrupts the equilibrium of cardiolipins (CLs), and directing CL synthesis promotes thrombosis. Using an untargeted metabolomics approach, approximately 3030 molecules were detected in zebrafish embryos exposed to 11 environmental chemicals and automatically clustered into a network. Interconnectivity among CLs and linoleates or isoxanthopterin was discovered through the highly consistent variations in the coregulated metabolites in the network. The chemical exposure resulted in significant upregulation of CLs through influencing the enzymatic activities of phospholipase A2, cardiolipin synthase, and lysocardiolipin acyltransferase. Consequently, metabolic disorders of CLs affected the levels of anticardiolipin antibodies, disrupted the homeostasis between platelet thromboxane A2 and endothelial prostacyclin, and promoted thrombotic events including heart ischemia and tachycardia. Our study thus reveals the common molecular mechanisms underlying the CL-induced thrombosis targeted by environmental exposures.

Investigation of antiphospholipid antibody syndrome markers in the etiology of recurrent miscarriage

This study aimed to determine the markers of antiphospholipid antibody syndrome (APS), which has an important place in the etiology of recurrent miscarriage, and to provide guidance for the treatment of the related disorders. This prospective observational study was performed on 120 female patients admitted to the Obstetrics and Gynecology outpatient clinics due to recurrent pregnancy loss. Blood samples were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) technique to find out the levels of APS-associated anticardiolipin (ACA), anti-beta2-glycoprotein I (aβ2GPI), anti-annexin V (aANXV), anti-prothrombin (aPT), and antiphosphatidylserine (aPS) antibodies. A statistically significant difference was found between increased age groups and the number of miscarriages (p=0.03, p