Anti‐protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation

Régnault, V.; Boehlen, Françoise; Özşahin, Hülya; Wahl, D.; Groot, Philip G. de; Lecompte, T.; Moerloose, Philippe de

doi:10.1111/j.1538-7836.2005.01270.x

Cited by 60 publications

(47 citation statements)

References 32 publications

(63 reference statements)

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“…In the early stages of inflammation, free PS also binds to apoptotic cells providing a platform for a PS-C4bBP complex that promotes phagocytosis of apoptotic cells. Interestingly, autoantibodyinduced PS deficiency has been observed in postinfectious purpura fulminans, 48 as well as in patients with systemic lupus erythematosis with excess inflammation. 49 TM is expressed by endothelial cells throughout the vasculature and plays a key role in simultaneously regulating coagulation and innate immunity.…”

Section: The Protein C-thrombomodulin Mechanismmentioning

confidence: 99%

Coagulation and innate immune responses: can we view them separately?

Delvaeye

Conway

2009

Blood

266

210

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The horseshoe crab is often referred to as a "living fossil," representative of the oldest classes of arthropods, almost identical to species in existence more than 500 million years ago. Comparative analyses of the defense mechanisms used by the horseshoe crab that allowed it to survive mostly unchanged throughout the millennia reveal a common ancestry of the coagulation and innate immune systems that are totally integrated-indeed, almost inseparable. In human biology, we traditionally view the hemostatic pathways and those regulating innate immune responses to infections and tissue damage as entirely separate entities. But are they? The last couple of decades have revealed a remarkable degree of interplay between these systems, and the linking cellular and molecular mechanisms are rapidly being delineated. In this review, we present some of the major points of intersection between coagulation and innate immunity. We attempt to highlight the potential impact of these findings by identifying recently established paradigms that will hopefully result in the emergence of new strategies to treat a range of inflammatory and hemostatic disorders. IntroductionThe most menacing challenge to survival that is faced by organisms throughout the animal kingdom is invasion by infections and foreign antigens-events that are frequently accompanied by trauma or a wound. Organisms have thus necessarily developed a variety of effective means to restrict and to fight infections, to contain wounds by limiting bleeding with clot formation, and to rapidly initiate healing. The coexistence of thrombosis with inflammatory responses supports the notion that common molecular mechanisms regulate these complex biologic systems. The last couple of decades have seen major progress in identifying cellular and molecular links between these systems.In this review, we consider some of the key pathways involved in hemostasis, innate immunity, and inflammation, and provide recent data that demonstrate how they are integrated. The interactions are multiple and complex, and present new challenges to identify those that are clinically relevant, with the promise of discovering novel and more effective therapies for a range of diseases. CoagulationThe coagulation system is characterized by the sequential, rapid, and highly localized activation of a series of serine proteases, culminating in the generation of thrombin, with subsequent conversion of fibrinogen into a fibrin clot. Tissue factor (TF) is the key initiator of coagulation (reviewed in Mackman 1 ), and is expressed primarily by subendothelial mural cells and adventitial fibroblasts in and around the vessel wall. Somewhat controversial, it may also be expressed at low levels by monocytes and neutrophils, and found circulating in microparticles and in a soluble form. 2 With vascular endothelial cell damage, TF is exposed to the circulation, and complexes with factor VII/VIIa, initiating activation of factors IX and X. Factor Xa converts prothrombin to thrombin in sufficient quantities to activat...

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Section: The Protein C-thrombomodulin Mechanismmentioning

confidence: 99%

Coagulation and innate immune responses: can we view them separately?

Delvaeye

Conway

2009

Blood

266

210

View full text Add to dashboard Cite

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“…Since this report, about 40 additional cases with severe protein S deficiency and transient presence of IgG antibodies against protein S have been reported [6][7][8][9]. The epitopes on protein S of these antibodies was reported by one study [10].…”

Section: Discussionmentioning

confidence: 74%

“…However, in children with varicella accompanied with purpura fulminans or thromboembolism events, the mean protein S IgG antibody levels were higher and mean protein S levels lower compared with children with uncomplicated varicella [8]. Severe protein S deficiency induced in vitro strong thrombin generation due to functional impairment of the protein C anticoagulant pathway [9]. The simultaneous presence of anticardiolipin antibodies may increase the hypercoagulability.…”

Section: Discussionmentioning

confidence: 97%

Acute renal cortical necrosis due to acquired antiprotein S antibodies

et al. 2009

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Although varicella is a common disease of childhood, renal complications are quite rare. We report here the interesting case of a-22 month-old boy exhibiting renal cortical necrosis related to an acquired protein S deficiency following varicella. Ten days after the vesicle eruption appearance, he presented with ecchymosed heels, oligoanuric kidney failure, anemia [hemoglobin (Hb) 78 g/L], schizocytosis (2.5%), but normal platelet count. Kidney sonography and magnetic resonance imaging evoked renal cortical necrosis. All together, these features suggested acquired protein S deficiency secondary to varicella. Strikingly, it was confirmed by a dramatic decrease in protein S plasma activity and a huge increase in immunoglobulin (Ig)G antibodies against protein S in the plasma. Anticoagulation therapy in addition with plasmapheresis and steroid pulses allowed a dramatic decrease in the antibodies against protein S and recovery of normal protein S activity. Undelayed diagnosis and treatment did not avoid kidney insufficiency but prevented life-threatening complications. In the light of this case report, protein S deficiency due to antibody inhibition should be carefully monitored anytime in the context of varicella when kidney insufficiency or necrosis occurs.

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“…Postvaricella purpura fulminans is a rare complication in children caused by acquired PC or PS deficiency (112). PS deficiency has also been described in patients with AIDS (113,114). Therapy with L-asparaginase may lead to decreased PC concentrations by decreasing its synthesis in the liver.…”

Section: Conditions Affecting Protein C and Protein S Levels; Acquirementioning

confidence: 99%

Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game

Bereczky

Kovács

Muszbek

2010

Clinical Chemistry and Laboratory Medicine

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Protein C (PC) and protein S (PS) are vitamin K-dependent glycoproteins that play an important role in the regulation of blood coagulation as natural anticoagulants. PC is activated by thrombin and the resulting activated PC (APC) inactivates membrane-bound activated factor VIII and factor V. The free form of PS is an important cofactor of APC. Deficiencies in these proteins lead to an increased risk of venous thromboembolism; a few reports have also associated these deficiencies with arterial diseases. The degree of risk and the prevalence of PC and PS deficiency among patients with thrombosis and in those in the general population have been examined by several population studies with conflicting results, primarily due to methodological variability. The molecular genetic background of PC and PS deficiencies is heterogeneous. Most of the mutations cause type I deficiency (quantitative disorder). Type II deficiency (dysfunctional molecule) is diagnosed in approximately 5%-15% of cases. The diagnosis of PC and PS deficiencies is challenging; functional tests are influenced by several pre-analytical and analytical factors, and the diagnosis using molecular genetics also has special difficulties. Large gene segment deletions often remain undetected by DNA sequencing methods. The presence of the PS pseudogene makes genetic diagnosis even more complicated. Clin Chem Lab Med 2010;48:S53-66.

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Anti‐protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation

Cited by 60 publications

References 32 publications

Coagulation and innate immune responses: can we view them separately?

Coagulation and innate immune responses: can we view them separately?

Acute renal cortical necrosis due to acquired antiprotein S antibodies

Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game

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