Current concepts on the pathogenesis of the antiphospholipid syndrome

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 422-430 ◽  
Author(s):  
Bill Giannakopoulos ◽  
Freda Passam ◽  
Soheila Rahgozar ◽  
Steven A. Krilis
Keyword(s):  
Experimental Evidence ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Peripheral Tolerance ◽  
The Core ◽  
Glycoprotein I ◽  
Antigenic Targets ◽  
Acquired Thrombophilia

Abstract The antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia. It is characterized by the core clinical manifestations of thrombosis, either venous or arterial, and in women it can also be associated with recurrent fetal loss. The detection of persistently elevated levels of antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the diagnosis to be made. The dominant antigenic targets in APS are beta 2-glycoprotein I (β2-GPI) and prothrombin. There is an accumulating body of experimental evidence that suggests that specific subgroups of aPL Abs may directly contribute to disease pathogenesis. This review critically examines the experimental evidence underlying the various propositions made to explain how these antibodies may predispose to disease in humans. Furthermore, it also examines the evidence relating to the immunologic mechanisms that may contribute to the breakage of peripheral tolerance in this disorder. Delineating the strengths and limitations of the experimental evidence accumulated thus far will hopefully stimulate further experimentation toward achieving the ultimate goal of precisely defining the dominant pathogenic mechanisms operational in APS. This may pave the way for the development of improved therapies.

Atherosclerosis and the antiphospholipid syndrome: A link unravelled?

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 140-143 ◽  
Author(s):  
Y Shoenfeld ◽  
D Harats ◽  
J George
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Dominant Role ◽  
Clinical Manifestations ◽  
Humoral Response ◽  
Arterial System ◽  
Glycoprotein I ◽  
Shock Proteins ◽  
Modified Forms ◽  
Progression Of Atherosclerosis

Atherosclerosis is a multifactorial disease that involves the arterial system. Recent data suggest that immune and autoimmune factors play a dominant role in mediating the progression of atherosclerosis. Among these factors, humoral response to modified forms of LDL and heat-shock proteins has been shown to be influential. The antiphospholipid syndrome (APS) entails clinical manifestations that result from a hypercoagulable state. Antibodies to phospholipids and to β2-glycoprotein I have been suggested to confer the tendency to thrombosis. In a set of recent studies, we have been able to show that generation of antiphospholipid antibodies in mice is associated with enhanced atherosclerosis. These findings imply that APS and atherosclerosis may share a common etiologic background, which may have direct implications for the management of both conditions.

scholarly journals Isolated IgA Anti-β2 Glycoprotein I Antibodies in Patients with Clinical Criteria for Antiphospholipid Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Raquel Ruiz-García ◽  
Manuel Serrano ◽  
José Ángel Martínez-Flores ◽  
Sergio Mora ◽  
Luis Morillas ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Clinical Manifestations ◽  
Diagnostic Systems ◽  
Clinical Criteria ◽  
Glycoprotein I ◽  
Standardized Diagnostic ◽  
Disease Present

Seronegative antiphospholipid syndrome (SNAPS) is an autoimmune disease present in patients with clinical manifestations highly suggestive of Antiphospholipid Syndrome (APS) but with persistently negative consensus antiphospholipid antibodies (a-PL). IgA anti-β2 Glycoprotein I (aB2-GPI) antibodies are associated with APS. However, they are not currently considered to be laboratory criteria due to the heterogeneity of published works and the use of poor standardized diagnostic systems. We have aimed to assess aPL antibodies in a group of patients with clinical manifestations of APS (C-APS) to evaluate the importance of the presence of IgA aB2GPI antibodies in APS and its relation with other aPL antibodies. Only 14% of patients with C-APS were positive for any consensus antibody, whereas the presence of isolated IgA aB2GPI antibodies was found in 22% of C-APS patients. In patients with arterial thrombosis IgA aB2GPI, antibodies were the only aPL antibodies present. Serologic profile in primary APS (PAPS) is different from systemic autoimmune disorders associated APS (SAD-APS). IgA aB2GPI antibodies are more prevalent in PAPS and IgG aB2GPI antibodies are predominant in SAD-APS. The analysis of IgA aB2GPI antibodies in patients with clinical manifestations of PAPS might avoid underdiagnosed patients and provide a better diagnosis in patients with SAD-APS. Laboratory consensus criteria might consider including analysis of IgA aB2GPI for APS diagnosis.

Anti-phospholipid antibody mediated fetal loss: still an open question from a pathogenic point of view

Lupus ◽  
2010 ◽  
Vol 19 (4) ◽  
pp. 453-456 ◽  
Author(s):  
PL Meroni ◽  
F. Tedesco ◽  
M. Locati ◽  
A. Vecchi ◽  
N. Di Simone ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Neutrophil Infiltration ◽  
Point Of View ◽  
Pathogenic Mechanisms ◽  
Inhibition Of Growth ◽  
Glycoprotein I ◽  
Open Question

Antiphospholipid antibodies (aPL) are associated with recurrent miscarriages and pregnancy complications, however their pathogenic mechanisms are still matter of research. Thrombotic events at the placental level cannot explain all of the clinical manifestations. It has been suggested that aPL may be responsible for a local acute inflammatory response mediated by complement activation and neutrophil infiltration eventually leading to fetal loss. However histological and immunohistological studies on human placental samples do support such a mechanism only in part and with no any clear relationship with the pregnancy outcome. A direct effect of aPL on both maternal and fetal placental tissues has been reported through the reactivity of the antibodies with beta2 glycoprotein I (β2GPI) expressed on the cell membranes. These events do not require an inflammatory response and can be in part related to the inhibition of growth factors favouring a physiological placentation. Understanding the different pathogenic mechanisms of aPL-associated miscarriages may help in improving our therapeutic approach particularly in recurrent cases not responsive to the usual treatment. Lupus (2010) 19, 453—456.

The significance of autoantibodies against β2-glycoprotein I

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 266-274 ◽  
Author(s):  
Philip G. de Groot ◽  
Rolf T. Urbanus
Keyword(s):  
Autoimmune Disease ◽  
Infectious Diseases ◽  
Antiphospholipid Syndrome ◽  
Plasma Protein ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Thrombotic Risk ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
History Of

AbstractThe antiphospholipid syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with a history of thrombosis and/or pregnancy morbidity, including fetal loss. APS is an autoimmune disease with a confusing name because the pathologic auto-antibodies are shown to be directed against the plasma protein β2-glycoprotein I and not against phospholipids. In fact, auto-antibodies that recognize phospholipids themselves are not associated with thrombosis but with infectious diseases. One of the intriguing questions is why autoantibodies against β2-glycoprotein I are so commonly found in both patients and the healthy. Several potential mechanisms have been suggested to explain the increased thrombotic risk in patients with these autoantibodies. In this overview, we will summarize our knowledge on the etiology of the autoantibodies, and we will discuss the evidence that identify autoantibodies against β2-glycoprotein I as the culprit of APS.

Non β2-Glycoprotein I Cofactors for Antiphospholipid Antibodies

Lupus ◽  
1996 ◽  
Vol 5 (5) ◽  
pp. 388-392 ◽  
Author(s):  
M Galli
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Protein C ◽  
Activated Protein C ◽  
Clinical Manifestations ◽  
Annexin V ◽  
Protein S ◽  
Thromboembolic Events ◽  
Glycoprotein I ◽  
Recurrent Abortions

The Antiphospholipid Syndrome is defined by the association between peculiar clinical manifestations, namely arterial and/or venous thrombosis, recurrent abortions and thrombocytopenia, and the antiphospholipid antibodies. These antibodies are directed to plasma proteins bound to anionic phospholipids or other anionic surfaces: so far, β2-glycoprotein I is the best known and characterized antiphospholipid ‘cofactor’ ( this issue is specifically treated in other parts of this journal). In recent years, such a role has been reported also for prothrombin, activated Protein C, Protein S, Annexin V, Thrombomodulin, high- and low-molecular weight kininogens. Anti-prothrombin antibodies are detected in approximately 50% of the antiphospholipid-positive patients; conversely, limited data are available regarding the prevalence the other antibodies. ‘Cofactors' are necessary for the expression of both the immunological and the functional properties of their respective antiphospholipid antibodies. In particular, the recognition of the calcium-mediated prothrombin/lipid complex by anti-prothrombin antibodies hampers prothrombin activation, thus causing the prolongation of the phospholipid-dependent coagulation reactions. The interaction between antiphospholipid antibodies and natural inhibitors of coagulation such as activated Protein C, its non-enzymatic accessory protein Protein S or Thrombomodulin might increase the risk to develop thromboembolic events. Similarly, the presence of antibodies to surface-bound Annexin V has been hypothesized to play a role in recurrent abortions and fetal deaths. However, to clearly establish whether and which antiphospholipid antibodies represent risk factors for the thromboembolic events of the antiphospholipid syndrome, further studies of their behaviour and properties as well as the identification and characterization of (possibly) other antibodies are required.

β2-Glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome

Blood ◽  
2010 ◽  
Vol 116 (8) ◽  
pp. 1336-1343 ◽  
Author(s):  
Çetin Ağar ◽  
Gwendolyn M. A. van Os ◽  
Matthias Mörgelin ◽  
Richard R. Sprenger ◽  
J. Arnoud Marquart ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Partial Thromboplastin Time ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Activated Partial Thromboplastin Time ◽  
Ample Evidence ◽  
Glycoprotein I ◽  
Open Conformation ◽  
Cryptic Epitope ◽  
Major Antigen

Abstract The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies in blood of patients with thrombosis or fetal loss. There is ample evidence that β2-glycoprotein I (β2GPI) is the major antigen for antiphospholipid antibodies. The autoantibodies recognize β2GPI when bound to anionic surfaces and not in solution. We showed that β2GPI can exist in at least 2 different conformations: a circular plasma conformation and an “activated” open conformation. We also showed that the closed, circular conformation is maintained by interaction between the first and fifth domain of β2GPI. By changing pH and salt concentration, we were able to convert the conformation of β2GPI from the closed to the open conformation and back. In the activated open conformation, a cryptic epitope in the first domain becomes exposed that enables patient antibodies to bind and form an antibody-β2GPI complex. We also demonstrate that the open conformation of β2GPI prolonged the activated partial thromboplastin time when added to normal plasma, whereas the activated partial thromboplastin time is further prolonged by addition of anti-β2GPI antibodies. The conformational change of β2GPI, and the influence of the autoantibodies may have important consequences for our understanding of the antiphospholipid syndrome.

scholarly journals Systemic Lupus Erythematosus and Antiphospholipid Syndrome

2014 ◽  
Vol 2 (3) ◽  
pp. 544-549
Author(s):  
Aleksandra Plavsic ◽  
Rada Miskovic ◽  
Sanvila Raskovic ◽  
Mirjana Bogic ◽  
Branka Bonaci Nikolic
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Autoimmune Disorder ◽  
Systemic Lupus ◽  
Vascular Thrombosis ◽  
Glycoprotein I ◽  
Independent Entity ◽  
Acquired Thrombophilia

Antiphospholipid syndrome is an autoimmune disorder defined as association of vascular thrombosis and/or pregnancy complications with presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin and anti-β2 glycoprotein I). It is the most common cause of acquired thrombophilia, and can occur as an independent entity or in relation with other diseases, especially systemic lupus erythematosus. Presence of antiphospholipid syndrome in systemic lupus erythematosus is additional vaso occlusive factor in already present inflammation, bringing further risk for thrombotic events. Clinical and serological manifestations of antiphospholipid syndrome and systemic lupus erythematosus are very similar, so possible connection for these two autoimmune disorders is assumed.

scholarly journals ANTIPHOSPHOLIPID SYNDROME

2017 ◽  
pp. 4-11
Author(s):  
E. V. Makarenko
Keyword(s):  
Blood Plasma ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Lupus Anticoagulant ◽  
Pregnancy Complication ◽  
Classification Criteria ◽  
Clinical Criteria ◽  
Glycoprotein I ◽  
Acquired Thrombophilia

Antiphospholipid syndrome is autoimmune acquired thrombophilia associated with the formation of antibodies to phospholipids, which is manifested by recurrent venous or arterial thrombosis and/or pathology of pregnancy. Antiphospholipid antibodies are a heterogeneous group of autoantibodies interacting with phospholipids, which are components of cell membranes and phospholipid-binding proteins of blood plasma. Antiphospholipid syndrome can affect vessels of any caliber and localization, with thrombosis accompanied by no morphological signs of inflammation in the wall of the vessel. Obstetrical pathology is manifested by loss of the fetus, which can occur at any time of pregnancy, as well as other complications of pregnancy, such as preeclampsia and placental insufficiency. Based on the classification criteria, antiphospholipid syndrome is diagnosed if one of the clinical criteria (thrombosis or pregnancy complication) and one of the laboratory criteria including the lupus anticoagulant, antibodies to cardiolipin or β2-glycoprotein I, are revealed. The main tactic of the treatment of patients with antiphospholipid syndrome is to prevent thrombosis. For this purpose, the traditional therapy with anticoagulants and antiaggregants is applied. In addition, new medicines are being developed and evaluated

scholarly journals The antiphospholipid syndrome: still an enigma

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Shruti Chaturvedi ◽  
Keith R. McCrae
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Basic Research ◽  
Laboratory Diagnosis ◽  
Pregnancy Morbidity ◽  
Common Causes

Abstract Antiphospholipid syndrome (APS) is defined by clinical manifestations that include thrombosis and/or fetal loss or pregnancy morbidity in patients with antiphospholipid antibodies (aPL). Antiphospholipid antibodies are among the most common causes of acquired thrombophilia, but unlike most of the genetic thrombophilias are associated with both venous and arterial thrombosis. Despite an abundance of clinical and basic research on aPL, a unified mechanism that explains their prothrombotic activity has not been defined; this may reflect the heterogeneity of aPL and/or the fact that they may influence multiple pro- and/or antithrombotic pathways. Antiphospholipid antibodies are directed primarily toward phospholipid binding proteins rather than phospholipid per se, with the most common antigenic target being β2-glycoprotein 1 (β2GPI) although antibodies against other targets such as prothrombin are well described. Laboratory diagnosis of aPL depends upon the detection of a lupus anticoagulant (LA), which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin and anti-β2-glycoprotein 1 antibodies. Indefinite anticoagulation remains the mainstay of therapy for thrombotic APS, although new strategies that may improve outcomes are emerging. Preliminary reports suggest caution in the use of direct oral anticoagulants in patients with APS-associated thrombosis. Based on somewhat limited evidence, aspirin and low molecular weight heparin are recommended for obstetrical APS. There remains a pressing need for better understanding of the pathogenesis of APS in humans, for identification of clinical and laboratory parameters that define patients at greatest risk for APS-related events, and for targeted treatment of this common yet enigmatic disorder.

scholarly journals Primary antiphospholipid syndrome in children: experience from two tertiary centres in South India

2019 ◽  
Vol 6 (2) ◽  
pp. 243
Author(s):  
Mahesh Janarthanan ◽  
Dhaarani Jayaraman ◽  
Julius Scott ◽  
M. S. Latha ◽  
Saravanan Margabandhu ◽  
...  
Keyword(s):  
Clinical Features ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Primary Antiphospholipid Syndrome ◽  
Retrospective Case ◽  
Case Record ◽  
Vascular Thrombosis ◽  
Immunologic Profile

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by the presence of episodes of vascular thrombosis, recurrent fetal loss and other clinical features in the presence of antiphospholipid antibodies. The aim of the study was to analyze the clinical manifestations and immunologic profile of children presenting with APS.Methods: Authors did a retrospective case record study of patients admitted with thrombotic events between September 2013 and August 2018 and identified patients with positive antiphospholipid antibodies. Children who had clinical features of active lupus were not included.Results: The clinical and immunologic profile of 7 pediatric patients presenting with APS over 5 years from 2013 to 2018 were analysed. Symptoms secondary to vascular thrombosis were limb swelling, stroke, gangrene of toes and Budd Chiari syndrome.Conclusions:APS though rare should be considered in the differential diagnosis of children presenting with thrombotic events. They need long term anticoagulants to prevent further episodes. 

Sign in / Sign up

Export Citation Format

Share Document