scholarly journals Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome

Blood ◽  
2006 ◽  
Vol 107 (11) ◽  
pp. 4375-4382 ◽  
Author(s):  
Gabriela Cesarman-Maus ◽  
Nina P. Ríos-Luna ◽  
Arunkumar B. Deora ◽  
Bihui Huang ◽  
Rosario Villa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Cell Surface Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Antigen ◽  
Healthy Individuals ◽  
Annexin 2

AbstractThe association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and β2-glycoprotein I (β2GPI), the main antigen for antiphospholipid antibodies. Here, we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies. Anti-A2 antibodies (titer > 3 SDs) were significantly more prevalent in patients with APS (22.6%; venous, 17.5%; arterial, 34.3%; and mixed thrombosis, 40.4%) than in healthy individuals (2.1%, P < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001). Anti–A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold ± 0.13-fold SE), blocked A2-supported plasmin generation in a tPAdependent generation assay (19%-71%) independently of β2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%. We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome.

Autoantibodies Against the Fibrinolytic Receptor, Annexin 2, in Antiphospholipid Syndrome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 134-134
Author(s):  
Gabriela Cesarman ◽  
Nina P. Ríos-Luna ◽  
Arunkumar B. Deora ◽  
Maria del Carmen Cravioto ◽  
Donato Alarcón-Segovia ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Umbilical Vein ◽  
Healthy Individuals ◽  
Endothelial Cell Surface ◽  
Glycoprotein I ◽  
Annexin 2

Abstract The association of thrombosis, obstetric morbidity, and hemocytopenias with antiphospholipid antibodies is termed antiphospholipid syndrome. Annexin 2 is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and beta-2-glycoprotein-I, the main antigen for antiphospholipid antibodies. Here we evaluate annexin 2 as a target antigen in antiphospholipid syndrome. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with antiphospholipid syndrome, 21 with non-autoimmune thrombosis, and 145 healthy individuals) were analyzed by ELISA and immunoblotting for antiphospholipid and annexin 2 antibodies. IgG was purified and the effect of anti-annexin 2 antibodies on human umbilical vein endothelial cell activation and cell surface plasmin generation were evaluated. Anti-annexin 2 antibodies (titer &gt;3SD) were significantly more prevalent in patients with antiphospholipid syndrome (22.6%, venous 17.5%, arterial 34.3% and mixed thrombosis 40.4%), than in healthy individuals (2.1%, p&lt;0.001), patients with non-autoimmune thrombosis (0%, p=0.017) or patients with lupus without thrombosis (6.3%, p&lt;0.001). Anti-annexin 2 antibodies enhanced the expression of tissue factor, a procoagulant protein, on endothelial cells (6.4 fold ± 0.13 SE), and blocked the fibrinolytic cofactor activity of purified placental annexin 2 in a tissue plasminogen activator-dependent plasmin generation assay (19 – 71%), independently of beta-2-glycoprotein-I. Similarly, cell surface plasmin generation on human umbilical vein endothelial cells was inhibited by 34–83%. We conclude that antibodies against the fibrinolytic receptor annexin 2 are significantly associated with thrombosis in antiphospholipid syndrome, and that anti-annexin 2 antibodies activate endothelial cells and inhibit endothelial cell surface-localized plasmin generation. We propose that these mechanisms contribute to the prothrombotic tendency in antiphospholipid syndrome.

Functional Analyses of Patient-derived IgG Monoclonal Anticardiolipin Antibodies Using In Vivo Thrombosis and In Vivo Microcirculation Models

2000 ◽  
Vol 84 (09) ◽  
pp. 388-395
Author(s):  
Xiaowei Liu ◽  
Ricardo Espinola ◽  
Tsawei Olee ◽  
Min Zhu ◽  
Nigel Harris ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Antiphospholipid Syndrome ◽  
Adhesion Molecule ◽  
Antiphospholipid Antibodies ◽  
Cell Function ◽  
Leukocyte Adhesion ◽  
Anticardiolipin Antibodies ◽  
Intercellular Adhesion Molecule ◽  
Enzyme Linked Immunosorbent Assay

SummaryAntiphospholipid antibodies (aPL) have been associated with thrombosis and pregnancy losses in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. It has been proposed that aPL may affect endothelial cell (EC) function and/or induce their activation, transforming their anticoagulant surface into procoagulant, thus predisposing to thrombosis. It has been proposed that aPL may affect EC cell function and/or induce their activation, transforming their anticoagulant surface into procoagulant, thus predisposing to thrombosis. This study proposes to test the hypotheses that some IgG anticardiolipins (IgG aCL) with thrombogenic properties in mice, exert their effects through activation of endothelium. We studied seven patient-derived monoclonal aCL for their thrombogenic properties in an in vivo pinch-induced thrombosis model, and their functional activities in activating EC by analyzing in vivo leukocyte adhesion to endothelium in microcirculation in venules in exposed murine cremaster muscle and in vitro adhesion molecule expression in cultured EC. The binding of the monoclonal aCL to EC was also tested. In addition to the previous identified thrombogenic IS2, four of the five new more IgG monoclonal aCL (from two patients) were found to be thrombogenic. Of these five thrombogenic aCL, three caused more in vivo leukocyte adhesion to EC in microcirculation, as compared to that induced by the H2 control human monoclonal IgG, and enhanced expression of adhesion molecules (particularly VCAM-1) on cultured EC. These data show that about 2/3 patientderived IgG monoclonal aCL are thrombogenic and suggest that some thrombogenic IgG aCL exert their effects through activating EC. Abbreviations: aCL, anticardiolipin antibodies; aPL, antiphospholipid antibodies; APS, antiphospholipid syndrome; CL, cardiolipin; dRVVT, dilute Russell’s viper venom time; EC, endothelial cells; ELISA, enzyme-linked immunosorbent assay; GP, glycoprotein; h, hour; HUVEC, human umbilicalvein endothelial cells; ICAM, intercellular adhesion molecule; KCT, kaolin clotting time; LA, lupus anticoagulant; PBS, phosphate-buffered saline; PL, phospholipid; sq, square; TBS, Tris-buffered saline; VCAM, vascular cell adhesion molecule; PMBC, peripheral mononuclear blood cells

Study of antiphospholipid antibodies by enzyme immunoassay and chemiluminescent methods in patients with antiphospholipid syndrome and systemic lupus erythematosus (preliminary data)

2021 ◽  
Vol 66 (9) ◽  
pp. 546-551
Author(s):  
F. A. Cheldieva ◽  
T. M. Reshetnyak ◽  
M. V. Cherkasova ◽  
A. M. Lila
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Preliminary Data ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serological Markers ◽  
Systemic Lupus

Antiphospholipid antibodies (aPL) are a family of different autoantibodies that lead to recurrent vascular thrombosis of any localization and caliber, and/or obstetric pathology - fetal loss. Serological markers of antiphospholipid syndrome (APS) include only three types of aPL - lupus anticoagulant (VA), antibodies to cardiolipin (aCL) classes IgG and IgM, antibodies to β2-glycoprotein1 (aβ2GP1) classes IgG and IgM. Medium and high levels of aCL and aß2HP1 (IgG and / or IgM) were selected as serological markers of APS in the 2006 classification criteria. However, the threshold of values used from low to moderately high levels has not been standardized. aPL standardization issues are still unresolved, resulting in heterogeneous results of the ongoing studies. The aim of the study was to assess the comparability IgG/IgM-aCL and IgG/IgM-ab2GP1 by enzyme-linked immunosorbent assay and chemiluminescent analysis in patients with APS with and without (systemic lupus erythematosus) SLE. The study included 70 patients (49 women and 21 men) with APS, of which 21 (30%) were with primary APS (pAPS) and 49 (70%) with APS in combination with SLE. All study participants underwent determination of IgG/IgM-aCL and IgG/IgM-aβ2GP1 by enzyme-linked immunosorbent. A study was performed by the chemiluminescent analysis: IgG/IgM-aCL - in 70 patients; IgG/IgM-aβ2GP1 - in 69 patients. Results. According to preliminary data, the determination of IgG-aCL and IgG-aβ2GP1 by the chemiluminescent analysis is informative in assessing positivity according to the manufacturer, compared with the enzyme-linked immunosorbent (p < 0.05). However, when taking into account the levels of antibody positivity determined by enzyme-linked immunosorbent, the level of positive values according to chemiluminescent analysis was much higher than the performance of the manufacturer.

scholarly journals POS0712 “EXTRA”- CRITERIA ANTIPHOSPHOLIPID ANTIBODIES IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOSUS (PRELIMINARY DATA)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 605.2-606
Author(s):  
F. Cheldieva ◽  
T. Reshetnyak ◽  
M. Cherkasova ◽  
N. Seredavkina ◽  
A. Lila
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Preliminary Data ◽  
Antiphospholipid Antibodies ◽  
Disease Duration ◽  
Past History ◽  
Igg Antibodies ◽  
Systemic Lupus ◽  
Pregnancy Morbidity

Background:The study of antiphospholipid antibodies (aPL), not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood.Objectives:To determine the frequency of detection of IgA-aCL and IgA-aβ2GP1 and IgG antibodies to β2GP1 domain 1 (IgG-aβ2GP1-D1) in patients with APS with and without SLE.Methods:ELISA and chemiluminescence assays (CMA) were used to test 63 sera of patients: 22 (35%) with primary APS (pAPS) and 41 (65%) patients with APS and with SLE (secondary APS (sAPS)), with mean age 38,0 [33,0 – 43,0] years and disease duration 4,0 [0,1 – 9,9]. Both methods were used to test of IgG/IgM-aCL and IgG/IgM-aβ2GP1. CMA was used for research IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GPI and IgG-aβ2GP1-D1. Of them 49 (78%) (18 – with pAPS; 31 – with sAPS) displayed major thrombotic events and 18 of 22 pregnant women had pregnancy morbidity in past history. Lupus anticoagulant (LA) positivity was in 9 out of 12 patients who had it determined. LA was not investigated due to anticoagulant therapy in the remaining 52 patients.Results:IgG/IgM-aCL and IgG/IgM-aß2GP1 were recorded in 44/18 and 50/17 patients by ELISA and in 55/19 and 59/16 by CMA, respectively.IgA-aCL positivity was found in 35 (56%) of 63 patients. Thirty IgA-positive patients were positive for IgG-aCL by ELISA: 22 – IgG-aCL – highly positive, 6 – medium positive and 2 – low positive patients. IgM-aCL by ELISA was detected in 13 (37%) of 35 IgA-aCL positive patients: 11 – highly positive, 1 – medium positive and 1 – low positive. IgA-aCL was combined with IgG-aCL in 34 patients and with IgM-aCL in 16 patients in the CMA. IgG-aß2GP1 in ELISA was detected in 32 patients with IgA-aCL (24 –highly positive, 5 – medium positive and 3 – low positive) and in 34 – in CMA. IgM-aß2GP1 was combined with IgA-aß2GP1 with the same frequency in both methods (in 13 patients).IgA-aß2GP1 was detected in 30 (48%) of 63 patients. They were combined with both IgG-aCL and IgG-aß2GP1 in all cases in both methods. IgM-aCL and IgM-aß2GP1 were detected in 14 and 11 of 30 patients with IgA-aß2GP1, respectively. The combination of IgA-aß2GP1 with IgG-aCL by ELISA was in 27 (in most cases highly positive – 20) and with IgM-aCL – in 10 (highly positive - 8). IgG-aß2GP1 was detected in 28 patients with IgA-aß2GP1 (high positive – 21) and in 11 patients with IgM-aß2GP1 (high positive –7).IgG-aß2GP1-D1 was revealed in 48 (76%) patients. It was combined with IgG-aCL – in 38, with IgM-aCL – in 15 patients by the ELISA. The combination of IgG-aß2GP1-D1 by CMA was as follows: with IgG-aCL – in 46, with IgM-aCL – in 17, and with IgA-aCL – in 33 patients. In most cases, IgG-aß2gp1-D1 was combined with highly positive aCL levels. IgG-aß2GP1-D1 positivity was associated with IgG-aß2GP1 positivity in 42 – by ELISA and 47 – by CMA, IgМ-aβ2GP1 – in 13 and 14 patients by ELISA and CMA, respectively, and IgA-aß2GP1 – in 29. Isolated IgG-aß2GP1-D1 positivity was not observed.Conclusion:The frequency of IgA-aCL detection was 56% (35 patients out of 63), IgA-aβ2GP1 – 48% (30 patients out of 63), IgG-aβ2GP1-D1 – 76% (48 patients out of 63). There was not isolated positivity of this “extra” criterial antibodies. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with highly positivity of IgG/IgM-aCL and IgG/IgM- aβ2GP1.Disclosure of Interests:None declared

scholarly journals MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells

2019 ◽  
Vol 20 (12) ◽  
pp. 3107 ◽  
Author(s):  
Mikel Aristorena ◽  
Eunate Gallardo-Vara ◽  
Matej Vicen ◽  
Mateo de Las Casas-Engel ◽  
Luisa Ojeda-Fernandez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Macrophage Polarization ◽  
Cell Surface Receptor ◽  
Soluble Form ◽  
Specific Marker ◽  
Good Resolution ◽  
Angiogenic Activity ◽  
Soluble Endoglin

Upon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good resolution (M-MΦ) of the inflammatory process. The functional activity of polarized MΦ is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MΦ that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the MΦ secretome involved in the shedding of soluble endoglin. We find that the GM-MΦ secretome contains metalloprotease 12 (MMP-12), a GM-MΦ specific marker that may account for the anti-angiogenic activity of the GM-MΦ secretome. Cell surface endoglin is present in both GM-MΦ and M-MΦ, but soluble endoglin is only detected in GM-MΦ culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MΦ and endothelial cells. These data demonstrate a direct correlation between GM-MΦ polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.

scholarly journals ABD-Derived Protein Blockers of Human IL-17 Receptor A as Non-IgG Alternatives for Modulation of IL-17-Dependent Pro-Inflammatory Axis

2018 ◽  
Vol 19 (10) ◽  
pp. 3089 ◽  
Author(s):  
Marie Hlavničková ◽  
Milan Kuchař ◽  
Radim Osička ◽  
Lucie Vaňková ◽  
Hana Petroková ◽  
...  
Keyword(s):  
Cell Surface ◽  
Clinical Manifestations ◽  
Cell Surface Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 17 ◽  
Normal Human Skin ◽  
High Affinity ◽  
Th 17 ◽  
Surface Receptor

Interleukin 17 (IL-17) and its cognate receptor A (IL-17RA) play a crucial role in Th17 cells-mediated pro-inflammatory pathway and pathogenesis of several autoimmune disorders including psoriasis. IL-17 is mainly produced by activated Th-17 helper cells upon stimulation by IL-23 and, via binding to its receptors, mediates IL-17-driven cell signaling in keratinocytes. Hyper-proliferation of keratinocytes belongs to major clinical manifestations in psoriasis. To modulate IL-17-mediated inflammatory cascade, we generated a unique collection of IL-17RA-targeting protein binders that prevent from binding of human IL-17A cytokine to its cell-surface receptor. To this goal, we used a highly complex combinatorial library derived from scaffold of albumin-binding domain (ABD) of streptococcal protein G, and ribosome display selection, to yield a collection of ABD-derived high-affinity ligands of human IL-17RA, called ARS binders. From 67 analyzed ABD variants, 7 different sequence families were identified. Representatives of these groups competed with human IL-17A for binding to recombinant IL-17RA receptor as well as to IL-17RA-Immunoglobulin G chimera, as tested in enzyme-linked immunosorbent assay (ELISA). Five ARS variants bound to IL-17RA-expressing THP-1 cells and blocked binding of human IL-17 cytokine to the cell surface, as tested by flow cytometry. Three variants exhibited high-affinity binding with a nanomolar Kd value to human keratinocyte HaCaT cells, as measured using Ligand Tracer Green Line. Upon IL-17-stimulated activation, ARS variants inhibited secretion of Gro-α (CXCL1) by normal human skin fibroblasts in vitro. Thus, we identified a novel class of inhibitory ligands that might serve as immunosuppressive IL-17RA-targeted non-IgG protein antagonists.

Determinants of Risk for Venous and Arterial Thrombosis in Primary Antiphospholipid Syndrome and in Antiphospholipid Syndrome with Systemic Lupus Erythematosus

2009 ◽  
Vol 36 (6) ◽  
pp. 1195-1199 ◽  
Author(s):  
ADRIANA DANOWSKI ◽  
MARIO NEWTON LEITÃO de AZEVEDO ◽  
JOSE ANGELO de SOUZA PAPI ◽  
MICHELLE PETRI
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Venous Thrombosis ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Pregnancy Loss ◽  
Fold Increase ◽  
Systemic Lupus ◽  
Hereditary Thrombophilia

Objective.Antiphospholipid syndrome (APS) is characterized by thrombosis (venous and arterial) and pregnancy loss in conjunction with the lupus anticoagulant, IgG or IgM anticardiolipin, or IgG or IgM anti-ß2-glycoprotein I. In most series, only a minority of patients with antiphospholipid antibodies develop a clinical manifestation.Methods.A cross-sectional study of consecutive patients in the Hopkins Lupus Center was performed. Interviews were done and records were reviewed for the following variables: gender, ethnicity, hypertension, triglycerides, cholesterol, smoking, diabetes mellitus, homocysteine, cancer, hepatitis C, hormone replacement therapy/oral contraceptives, hereditary thrombophilia, anticardiolipin antibodies IgG, IgM and IgA, and lupus anticoagulant (LAC). Our aim was to identify risk factors associated with thrombosis and pregnancy loss in patients with antiphospholipid antibodies.Results.A total of 122 patients (84% female, 74% Caucasian) were studied. Patients were divided into 3 groups: primary APS, APS associated with systemic lupus erythematosus, and patients with systemic lupus erythematosus (SLE) with antiphospholipid antibodies but no thrombosis or pregnancy loss. Venous thrombosis was associated with high triglycerides (p = 0.001), hereditary thrombophilia (p = 0.02), anticardiolipin antibodies IgG > 40 (p = 0.04), and LAC (p = 0.012). Hypertriglyceridemia was associated with a 6.4-fold increase, hereditary thrombophilia with a 7.3-fold increase, and anticardiolipin IgG > 40 GPL with a 2.8-fold increase in the risk of venous thrombosis. Arterial thrombosis was associated with hypertension (p = 0.008) and elevated homocysteine (p = 0.044). Hypertension was associated with a 2.4-fold increase in the risk of arterial thrombosis. No correlations were found for pregnancy loss.Conclusion.The frequency of thrombosis and pregnancy loss is greater in APS associated with SLE than in primary APS. Risk factors differ for venous and arterial thrombosis in APS. Treatment of hypertension may be the most important intervention to reduce arterial thrombosis. Elevated triglycerides are a major associate of venous thrombosis, but the benefit of treatment is not known. Hereditary thrombophilia is an associate of venous but not arterial thrombosis, making it cost-effective to investigate only in venous thrombosis.

scholarly journals Shiga Toxin 2 Reduces Complement Inhibitor CD59 Expression on Human Renal Tubular Epithelial and Glomerular Endothelial Cells

2013 ◽  
Vol 81 (8) ◽  
pp. 2678-2685 ◽  
Author(s):  
Silvia Ehrlenbach ◽  
Alejandra Rosales ◽  
Wilfried Posch ◽  
Doris Wilflingseder ◽  
Martin Hermann ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Shiga Toxin ◽  
Human Kidney ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Protein Levels ◽  
Glomerular Endothelial Cells ◽  
Shiga Toxin 2 ◽  
Renal Tubular

ABSTRACTInfections with enterohemorrhagicEscherichia coli(EHEC) are a primary cause of hemolytic-uremic syndrome (HUS). Recently, Shiga toxin 2 (Stx2), the major virulence factor of EHEC, was reported to interact with complement, implying that the latter is involved in the pathogenesis of EHEC-induced HUS. The aim of the present study was to investigate the effect of Stx2 on the expression of membrane-bound complement regulators CD46, CD55, and CD59 on proximal tubular epithelial (HK-2) and glomerular endothelial (GEnC) cells derived from human kidney cells that are involved in HUS. Incubation with Stx2 did not influence the amount of CD46 or CD55 on the surface of HK-2 and GEnC cells, as determined by fluorescence-activated cell sorter analysis. In contrast, CD59 was significantly reduced by half on GEnC cells, but the reduction on HK-2 cells was less pronounced. With increasing amounts of Stx2, reduction of CD59 also reached significance in HK-2 cells. Enzyme-linked immunosorbent assay analyses showed that CD59 was not present in the supernatant of Stx2-treated cells, implying that CD59 reduction was not caused by cleavage from the cell surface. In fact, reverse transcription-quantitative PCR analyses showed downregulation of CD59 mRNA as the likely reason for CD59 cell surface reduction. In addition, a significant increase in terminal complement complex deposition on HK-2 cells was observed after treatment with Stx2, as a possible consequence of CD59 downregulation. In summary, Stx2 downregulates CD59 mRNA and protein levels on tubular epithelial and glomerular endothelial cells, and this downregulation likely contributes to complement activation and kidney destruction in EHEC-associated HUS.

Correlation between Osteoprotegerin Levels and Antiphospholipid Syndrome Parameters

2019 ◽  
Author(s):  
Simona Caraiola ◽  
Alina Dima ◽  
Ciprian Jurcut ◽  
Ruxandra Jurcut ◽  
Cristian Baicus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
High Serum ◽  
Systemic Lupus ◽  
Clinical Events ◽  
Double Stranded Dna ◽  
Female Data

Abstract Objective To identify the osteoprotegerin (OPG) correlates with antiphospholipid syndrome (APS) parameters. Methods Our cohort included 40 patients with primary APS disease associated with systemic lupus erythematosus (SLE) (mean age, 43.7 years; 87% female). Data on cardiovascular risk factors and specific clinical events in APS were collected. Then we tested OPG and 10 criteria and noncriteria antiphospholipid antibodies (aPLs) on preserved specimens in all cases. Results A total of 26 patients (65%) had high serum OPG levels. Patients with high OPG were mostly overweight. In patients with SLE, the OPG levels were associated with anti–double-stranded DNA (anti-dsDNA) and anti-Sm titers. However, we did not find significant correlations of the OPG with any of the 10 aPLs tested. Also, we found no relationship regarding venous APS events. Conclusion In APS, high OPG levels are not linked to serum aPL expression.

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