Prevalence and Clinical Correlation of Anti-Phospholipid–Binding Protein Antibodies in Anticardiolipin-Negative Patients With Systemic Lupus Erythematosus and Women With Unexplained Recurrent Miscarriages

2005 ◽  
Vol 129 (1) ◽  
pp. 61-68
Author(s):  
Nicola Bizzaro ◽  
Elio Tonutti ◽  
Danilo Villalta ◽  
Marilina Tampoia ◽  
Renato Tozzoli

Abstract Context.—Anti-phospholipid antibodies (aPL) are a heterogeneous group of autoantibodies, the presence of which is associated with thrombotic events and miscarriage. Objective.—To establish whether antibodies directed against phospholipid-binding plasma proteins such as β2-glycoprotein I (β2GPI), prothrombin (PT), and annexin V (Anx V) constitute a risk factor for thromboembolism in patients with systemic lupus erythematosus (SLE) and for miscarriage in women with recurrent pregnancy loss (RPL), independently of the presence of the classic anticardiolipin (aCL) antibodies, and whether their determination together with that of aCL would help to increase the diagnostic sensitivity of aPL tests. Design.—The prevalence of various antibodies directed toward phospholipids (CL and other anionic phospholipids [APL]) and phospholipid-binding proteins (β2GPI, PT, and Anx V) was determined by immunoenzymatic methods in 311 serum samples. Patients.—Twenty-five patients with aCL-positive primary anti-phospholipid syndrome (pAPS); 89 patients with SLE, 23 of whom had thrombotic complications (SLE/APS) and 66 of whom had no thrombosis; and 77 women with unexplained recurrent pregnancy loss comprised our study group. One hundred twenty healthy subjects matched for age and sex were studied as the control group. Results.—Immunoglobulin (Ig) G and/or IgM aAPL, anti-β2GPI, anti-PT, and IgG anti-Anx V antibodies were detected in 25 (100%), 20 (80%), 15 (60%), and 6 (24%), respectively, of the 25 aCL-positive pAPS patients; IgG and/or IgM aCL, aAPL, anti-β2GPI, anti-PT, and IgG anti-Anx V antibodies were detected in 33 (37%), 42 (47%), 31 (35%), 40 (45%), and 12 (13%) of the 89 SLE patients, respectively. Of the 56 SLE patients who proved to be aCL negative, anti-β2GPI was present in 3 patients (5%), anti-PT in 13 (23%) patients, and anti-Anx V in 5 (9%) patients. In the subset of 23 SLE/APS patients, IgG anti-PT prevalence was higher than that of the other autoantibodies (87% vs 70% aCL, 66% aAPL, 57% anti-β2GPI, and 4% anti-Anx V), and in 26% of cases, IgG anti-PT was the only antibody present. Anti-PT had a slightly lower specificity than aCL (46% vs 49%); however, the occurrence of both antibodies brought the specificity to 92.4%. The highest risk for thrombosis in SLE patients was associated with the presence of IgG anti-PT antibody (odds ratio [OR] 15.3, P < .001, vs 6.5 aCL, 3.5 aAPL, 3.4 anti-β2GPI, 0.2 anti-Anx V). Fifty-one of the 77 women with recurrent pregnancy loss were negative for all antibodies investigated; the prevalence of IgG and/or IgM aCL, aAPL, anti-β2GPI, anti-PT, and IgG anti-Anx V antibodies was 6% (5), 12% (9), 6% (5), 16% (12), and 17% (13), respectively. Of the 67 aCL-negative women, none had anti-β2GPI antibodies, 7 (11%) were anti-PT positive, and 13 (19%) were anti-Anx V positive. In the subgroup of 26 recurrent pregnancy loss patients who had at least one antibody, anti-Anx V was present in 50% of cases (in 42% as the sole antibody) and was the only antibody significantly associated with miscarriage (P = .02). Conclusions.—The results of this study indicate that it is useful to measure anti-PT antibodies in addition to the more widely used aCL and anti-β2GPI antibodies in the prognostic evaluation of SLE patients for the risk of thrombosis, and the results also confirm that anti-Anx V antibodies may play an important role in recurrent pregnancy loss.

Open Medicine ◽  
2010 ◽  
Vol 5 (1) ◽  
pp. 6-11
Author(s):  
Marta Baleva ◽  
Maria Hristova ◽  
Krasimir Nikolov

AbstractAnti-annexin A5 antibodies are directed against annexin A5 — a phospholipid-binding protein that belongs to the ubiquitous annexin family. These antibodies were first discovered in 1994 by Matsuda et al. in women with recurrent fetal loss or preeclampsia and in patients with systemic lupus erythematosus and positive lupus anticoagulant and/or anticardiolipin antibodies. Since then anti-annexin A5 antibodies have been the focus of research. In addition to their well known prothrombotic and procoagulant activities the authors discuss the involvement of these antibodies in the pathogenesis of antiphospholipid syndrome, recurrent pregnancy loss, systemic lupus erythematosus and other immune and non-immune disorders. Controversial reports are presented and a possible interpretation of the results is given. The authors suggest the significance of anti-annexin A5 antibodies as an additional diagnostic marker and discuss the necessity of more extensive research on their clinical significance.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3523
Author(s):  
Agnieszka Nowak ◽  
Brygida Przywara-Chowaniec ◽  
Aleksandra Damasiewicz-Bodzek ◽  
Dominika Blachut ◽  
Ewa Nowalany-Kozielska ◽  
...  

Systemic lupus erythematosus (SLE) is characterized by abnormal action of the immune system and a state of chronic inflammation. The disease can cause life-threatening complications. Neoepitopes arising from interdependent glycation and oxidation processes might be an element of SLE pathology. The groups included in the study were 31 female SLE patients and 26 healthy female volunteers (the control group). Blood serum samples were obtained to evaluate concentrations of advanced glycation end-products (AGEs), carboxymethyllysine (CML), carboxyethyllysine (CEL), pentosidine, and a soluble form of the receptor for advanced glycation end-products (sRAGE). Compared to a healthy control group, the SLE patients exhibited a higher concentration of AGEs and a lower concentration of sRAGE in serum. There were no statistically significant differences in serum CML, CEL, and pentosidine concentrations between the groups. Therefore, SLE patients could be at risk of intensified glycation process and activation of the proinflammatory receptor for advanced glycation end-products (RAGE), which could potentially worsen the disease course; however, it is not clear which compounds contribute to the increased concentration of AGEs in the blood. Additionally, information about the cigarette smoking and alcohol consumption of the study participants was obtained.


Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1551.1-1552
Author(s):  
V. Mazurov ◽  
O. Shadrivova ◽  
M. Shostak ◽  
L. Martynova ◽  
M. Tonkoshkur ◽  
...  

Background:Invasive aspergillosis (IA) is a severe opportunistic infection that is not well understood in rheumatological patients.Objectives:To study risk factors, etiology, clinical manifestations and results of treatment of IA in adult rheumatological patients.Methods:Retrospective analysis of 830 patients (1998-2019) with “proven” and “probable” IA (EORTC / MSG, 2019), adults - 699 (84%). The main group included 18 (3%) adult rheumatological patients with IA, a control group included 610 (87%) adult hematological patients. Rheumatological patients were older, the average age was 59 years (21–75) vs 45 years (18–79), p = 0.005, and among them there were more women – 56% vs 42%, p = 0.01.Results:In rheumatological patients with IA, underlying diseases were ANCA-associated vasculitis (28%), granulomatosis with polyangiitis (22%), periarteritis (11%), systemic lupus erythematosus (22%), rheumatic heart disease (11%) and ankylosing spondylitis (6%). In the control group, underlying diseases were acute leukemia (45%), lymphomas (34%), chronic leukemia (9%), multiple myeloma (7%), myelodysplastic syndrome (3%), and other hematological diseases (2%).The main risk factors for IA development in rheumatological patients were: systemic steroids use (89% vs 69%), prolonged lymphocytopenia (76% vs 65%, median - 14 vs 12 days), treatment in ICU (44% vs 18%, p = 0.01), acute or chronic renal failure (39% vs 1%, p = 0.0008) and immunosuppressive therapy (28% vs 25%). Severe neutropenia was noted significantly less frequently (18% vs 83%, p = 0.0001). Additional risk factors were decompensated diabetes mellitus (17% vs 2%, p = 0.004), previous surgery (17% vs 1%, p = 0.001) and organ transplantation (6% vs 0%). In rheumatological patients, lung (83% vs 98%, p = 0.0001) and ≥2 organs (6% vs 8%) involvement were less common. Heart (11% vs 0%), sinuses (6% vs 5%) and central nervous system (6% vs 4%) involvement more often developed. In rheumatological patients, respiratory failure (61 vs 37%, p = 0.03), hemoptysis (28% vs 7%, p = 0.0001) and chest pain (17% vs 7%, p = 0, 04) were noted more often, less often - fever ≥380С (67% vs 85%, p = 0.01) and cough (61% vs 70%). CT signs of lung damage were similar in both groups, but rheumatologic patients were more likely to show an «air crescent» sign and / or destruction cavity (44% vs 10%, p = 0.0001). In rheumatologic patients, IA was more often confirmed by isolation ofAspergillusspp. from BAL (80% vs 45%, p = 0.005) and by histological examination (22% vs 7%, p = 0.01). The main pathogens wereA. fumigatus(50% vs 43%),A. niger(29% vs 32%), andA. flavus(14% vs 17%).Rheumatological patients were less likely to receive antifungal therapy 89% vs 99%, p = 0,0003. The main drug in both groups was voriconazole. The overall 12-week survival did not significantly differ between groups, but was lower in rheumatological patients with IA (69% vs 81%).Conclusion:In rheumatological patients, invasive aspergillosis more often developed at an older age, mainly in women. The main background diseases were ANCA-associated vasculitis, granulomatosis with polyangiitis, and systemic lupus erythematosus. Typical risk factors were steroids and immunosuppressants use, prolonged lymphocytopenia, ICU stay, and renal failure. The main causative agents wereA. fumigatus,A. niger, andA. flavus. The main localization of infection were lungs. Respiratory failure, hemoptysis and heart involvement were typical. The overall 12-week survival of rheumatological patients with invasive aspergillosis was 69%.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1038.2-1039
Author(s):  
M. Kaleda ◽  
M. Krylov ◽  
I. Nikishina

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a significant genetic predisposition. Recent studies have identified STAT4 (signal transducers and transcription activators 4) as a susceptibility gene for SLE.Objectives:To investigate the hypothesis of the association of STAT4 rs7574865 G/T polymorphism with the predisposition to SLE in children and its relationship with some of SLE manifestations.Methods:The case-control pilot study included 143 children (39 with SLE and 103 healthy unrelated volunteers as a control group). Diagnosis of SLE was based on 2012 SLICC criteria. STAT4 rs7574865 G/T polymorphism was investigated using allele-specific real-time polymerase chain reaction (RT-PCR).Results:The group of pts with SLE consisted of 29 girls and 10 boys, with an average age of 11.8±3.7 years (from 3 to 17 years) and an average disease duration of 4.1±2.4 years. 79.5% pts had acute cutaneous lupus at the onset, 46.1% - nonscarring alopecia, 71.8% - arthritis, 23.1% - oral and nasal ulcers, 23.1% - serositis, 43.6% - renal involvement, 35.9% –neuropsychiatric disorders. Leucopenia/lymphopenia was found in 71.8% of pts, thrombocytopenia – in 23,1%. ANA were detected in 100% pts, anti-dsDNA – in 79.5%, anti-Sm – in 31.6%, antiphospholipid antibodies - in 7,3%, hypocomplementemia – in 61.5%, positive direct Coombs test – in 35.9 %. Macrophage activation syndrome at the onset was documented in 15.4 % of pts. The distribution of rs7574865 genotypes in the control group showed no significant deviations from the Hardy-Weinberg equilibrium. The distribution of genotype frequencies among pts had statistically significant differences compared to the control (χ2=12.95, p=0.0015): GG-30.8% and 63.1% (p=0.001), GT-56.4% and 33.0% (p=0.018), TT-12.8% and 3.9% (p=0.114), GT+TT - 69.2% and 36.9% (p=0.0005). The frequency of the mutant STAT 4 allele T (polymorphism), was significantly higher in the SLE group than in the control group (41% and 20.4%, respectively; p=0.0007). We identified an association of the T allele with some clinical, laboratory, and immunological disorders in SLE: arthritis (OR 3.9, p=0.0002), acute cutaneous lupus (OR 2.47, p=0.003), nonscarring alopecia (OR 3.12, p=0.002), renal involvement (OR 2.42, p=0.022), leucopenia (OR 2.72, p=0.003), thrombocytopenia (OR 4.88, p=0.002), anti-dsDNA (OR 2.82, p=0.0006), hypocomplementemia (OR 2.34, p=0.012), positive direct Coombs test (OR 3.38, p=0.002).Conclusion:Our pilot study confirmed that the STAT4 rs7574865 G/T polymorphism was associated with the risk of SLE in children and some of SLE manifestations.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 235.2-235
Author(s):  
J. Y. E. Lee ◽  
A. Mendel ◽  
I. Malhamé ◽  
S. Bernatsky ◽  
E. Vinet

Background:Pregnant women with systemic lupus erythematosus (SLE) are at high risk of preeclampsia, leading to substantial maternal and fetal morbidity. Aspirin reduces preeclampsia risk but recent studies suggest aspirin is used only in a minority of SLE pregnancies. There is an urgent need to improve preeclampsia counselling and management in this vulnerable population.Objectives:We are conducting the PREPARE (PREeclamPsia knowledge & Aspirin adheRence in lupus prEgnancies) trial, a randomized controlled trial (RCT) evaluating an educational tool on preeclampsia knowledge and aspirin adherence among pregnant women with SLE. We present preliminary analyses of the effect of this tool on preeclampsia knowledge.Methods:Consecutive pregnant SLE women are recruited until the 16th gestational week at 5Canadian Systemic Lupus International Collaborating Clinics centres (i.e. Montreal, Halifax, Quebec, Winnipeg, and Calgary) since 05/2018. Subjects are randomly assigned to receive either the specifically-designed educational tool (intervention group) or standard of care (control group). At baseline (i.e. first trimester) and second trimester visits, the participants complete self-administered preeclampsia knowledge questionnaires (scored out of 30 by the research team blinded to the intervention). We restricted the current analysis to participants enrolled in Montreal (accounting for nearly half of the total planned sample size). We performed a univariate linear regression analysis to assess the effect of the educational tool on preeclampsia knowledge (i.e. mean score difference between the two groups from baseline to second trimester visit).Results:Thirty-three pregnant SLE women were included in the study, among which 16 were exposed to the intervention and 17 were unexposed. Baseline characteristics were well balanced between the two groups with similar mean maternal age between intervention group (32.2 years, standard deviation, SD, 4.6) and control group (34.1 years, SD 4.2) and identical proportion of subjects with post-secondary education (i.e. 80%). The difference in mean preeclampsia knowledge scores between second trimester and baseline visits in the intervention group was 4.4 points (95% CI -0.1, 9.0) and in the control group was 1.5 points (95% CI -2.7, 5.7). The mean difference in knowledge scores (from baseline to second trimester) for those receiving the educational tool was 2.7 points higher (95% CI -1.5, 6.9) than those receiving standard of care.Conclusion:Approximately midway into the PREPARE trial, we observed a trend for improvement in preeclampsia knowledge from the baseline to the second trimester visit in pregnant women with SLE who received a specifically-designed educational tool compared to the control group, although the CIs included the null. Our RCT is well-poised to provide a new evidence-based approach to improve preeclampsia knowledge in pregnant women with SLE, which could help to optimize aspirin use and outcomes in this vulnerable population.References:[1]Schramm AM, Clowse ME. Aspirin for prevention of preeclampsia in lupus pregnancy. Autoimmune Dis. 2014;2014:920467. doi:10.1155/2014/920467[2]Bujold E, Roberge S, Lacasse Y, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol. 2010;116(2 Pt 1):402-414. doi:10.1097/AOG.0b013e3181e9322a[3]Andreoli L, Bertsias GK, Agmon-Levin N, et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017 Mar;76(3):476–85. doi: 10.1136/annrheumdis-2016-209770.[4]Mendel A, Bernatsky SB, Hanly JG, et al. Low aspirin use and high prevalence of preeclampsia risk factors among pregnant women in a multinational SLE inception cohort. Ann Rheum Dis. 2019;78(7):1010-1012. doi:10.1136/annrheumdis-2018-214434Disclosure of Interests:None declared.


2003 ◽  
Vol 64 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Antonio Amoroso ◽  
Anna P Mitterhofer ◽  
Flavia Del Porto ◽  
Pierluigi Garzia ◽  
Gianni M Ferri ◽  
...  

2006 ◽  
Vol 95 (01) ◽  
pp. 94-99 ◽  
Author(s):  
Gino Alfaro ◽  
Manuela Goycoolea ◽  
Teresa Quiroga ◽  
Mauricio Ocqueteau ◽  
Loreto Massardo ◽  
...  

SummaryThe risk for thrombosis is significantly increased in systemic lupus erythematosus (SLE), affecting both venous and arterial vessels. Activated platelets are known to participate in thrombus formation and growth. A general feature of activated cells is the shedding of microparticles (MP) which support coagulation by exposure of negatively charged phospholipids and possibly tissue factor (TF). In this work we characterized circulating MP in patients with SLE and their relationship with a procoagulant state. Thirty patients with SLE (aged 15–72 years, mean age 38 years) and 20 healthy controls (aged 22–54 years, mean age 34 years) were studied; patients fulfilled 4 revised criteria for SLE. The number and cellular source of circulating MP were determined by flow cytometry using double labeling with specific monoclonal antibodies and annexin V. Thrombin generation was measured as the endogenous thrombin potential (ETP) without the addition of exogenous phospholipids and TF; under these conditions the generation of thrombin depended directly on the number of MP present in plasma. Thrombin anti-thrombin (TAT) and plasmin-antiplasmin (PAP) complexes were measured by ELISA. Compared to the controls, circulating MP were significantly elevated in the patient group (1218 ± 136 vs 653 ± 74 x103/ml plasma, p: 0.0007). In both groups, most of these MP were of platelet origin (927± 131 vs 517 ± 72 x103/ml plasma, p:0.009 ). ETP was higher among patients as compared to the controls (804± 64 vs 631 ± 37 nM thrombin, p: 0.025). Plasma levels of TAT in patients and controls were 3.4 ± 0.8 and 1.4 ± 0.5 µg/L, respectively (p:0.04), and of PAP complexes were 62.5 ± 14 and 24.05± 2.5 µg/ml, respectively (p: 0.014).The number of platelet-derived MP correlated significantly with thrombin generation (r: 0.42; p: 0.038) and TAT levels (r: 0.40; p: 0.035).We did not find an association of circulating MP with disease activity nor with the presence of antiphospholipid antibodies. The increased number of circulating platelet-derived microparticles and their association with high ETP and activation of the coagulation system suggest that these microparticles play an important role in the pathogenesis of the prothrombotic state in SLE patients.


2002 ◽  
Vol 90 (3_part_2) ◽  
pp. 1091-1096 ◽  
Author(s):  
Grant L. Iverson

Accurate identification of depression in patients with systemic lupus erythematosus (SLE) is particularly complicated because the vegetative symptoms of depression also reflect core features of this autoimmune disease. Self-reported symptoms in patients with SLE ( n = 103) and community control subjects ( n = 136) were examined with the British Columbia Major Depression Inventory and the Beck Depression Inventory-II. The patients with lupus obtained higher scores on most items of the former inventory. A logistic regression analysis assessed whether a subset of these items were uniquely related to group membership. Clinically significant fatigue was much more common in patients with lupus than in the control group. Two items relating to sleep disturbance also entered the equation as unique predictors. The three-variable model resulted in 85% of the control subjects and 66% of the patients being correctly classified. A subset of patients with depression, according to the Beck inventory (17 or higher), were selected ( n = 41). Their most frequently endorsed symptoms on the British Columbia Inventory were fatigue (90.2%), trouble falling asleep (70.7%), cognitive difficulty (61%), and psychomotor slowing (58.5%). Only 29.3% reported significant sadness. 15% of these subjects were classified as not depressed, 46% as possibly depressed, and 39% as probably depressed on the British Columbia Inventory. It is advisable to assess whether patients are experiencing significant sadness or loss of interest before concluding that a high score on a screening test corresponds to probable depression.


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