Monoclonal immunoglobulin M lambda coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant.

Thiagarajan, Perumal; Shapiro, Sandor S.; Marco, Luigi De

doi:10.1172/jci109869

Cited by 377 publications

(147 citation statements)

References 44 publications

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“…In terms of j3,-GPI dependence, the specificity of our monoclonal aCL was clearly different from that of aCL found in patients with infectious diseases without the symptoms of the APS. Thiagarajan et a1 (35) first reported the crossreactivity of monoclonal IgM paraprotein with anionic PLs. Rauch and coworkers (25) reported that part of human monoclonal antibodies with LA activity crossreacted not only with PS, but also with PE, PI, and PC.…”

Section: Discussionmentioning

confidence: 99%

β₂‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

Ichikawa

Khamashta

Koike

et al. 1994

Arthritis & Rheumatism

147

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Objective. To elucidate the specificity of anticardiolipin antibodies (aCL) from patients with the antiphospholipid syndrome (APS) to various phospholipids (PLs), DNA, and β2‐glycoprotein I (β2‐GPI). Methods. Five monoclonal aCL were established from peripheral blood lymphocytes of 3 patients with the APS. The reactivity of monoclonal aCL with various PLs, with DNA, and with β2‐GPI was examined by enzyme‐linked immunosorbent assay (ELISA). Results. All of the monoclonal aCL bound to anionic PLs, only in the presence of β2‐GPI. Neither monoclonal aCL nor β2‐GPI bound to DNA. Monoclonal aCL bound to solid‐phase β2‐GPI on polystyrene ELISA plates that had carboxyl groups on their surface, but did not react with solid‐phase β2‐GPI on ordinary polystyrene plates. A mixture of β2‐GPI and CL inhibited the binding of monoclonal aCL to β2‐GPI, but CL or β2‐GPI alone did not. Conclusion. Monoclonal aCL may recognize a cryptic epitope, which appears as a result of β2‐GPI binding to anionic PLs or to polystyrene with carboxyl groups.

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Section: Discussionmentioning

confidence: 99%

β₂‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

Ichikawa

Khamashta

Koike

et al. 1994

Arthritis & Rheumatism

147

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“…On the basis of this mechanism of anticoagulation, VAC can be assigned to the group of anticoagulants which interfere with the accessory components of procoagulant complexes. Activated protein C 111,121, some phospholipases A2 [13] and some Lupus anticoagulant species [14] already belong to this class. Among them VAC is unique in binding in a calcium-dependent way, reversibly to negatively charged phospholipids, and does not anticoagulate through a proteolysis.…”

Section: Discussionmentioning

confidence: 99%

Purification and characterization of a novel protein from bovine aorta that inhibits coagulation

Reutelingsperger¹,

Kop²,

Hornstra³

et al. 1988

European Journal of Biochemistry

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A novel inhibitor of blood coagulation has been isolated from the intima of bovine aorta. The inhibitor, vascular anticoagulant (VAC), has been purified to an active fraction that contains two Coomassie-blue-staining bands (Mr = 34000 and M , = 32000, as judged by sodium dodecyl sulfate/polyacrylamide electrophoresis). Both bands are single-chain proteins, having no glycoprotein features. Furthermore, they do not contain any detectable 4-carboxyglutamic acid residues. Both proteins have an identical isoelectric pH of approximately 4.5. VAC binds in the presence of calcium ions to a bilayer consisting of 20% dioleoylglycerophosphoserine and 80% dioleoylglycerophosphocholine with a Kd = 6 nM. The binding is dependent on the calcium concentration: halfsaturation of binding occurs at a calcium concentration of 0.8 mM. The binding is completely reversible with EDTA. Furthermore the phospholipid/VAC ratio at saturation was n = 112 and n = 32 mol/mol for 0.5 mM Ca2+ and 2 mM Ca2+, respectively. Binding does not occur between VAC and pure dioleoylglycerophosphocholine. In a system with purified coagulation factors VAC inhibits the activation of prothrombin by factor X, and calcium only in the presence of negatively charged phospholipids. VAC decreases the V,,, and increases the K, of the factor-X,-catalyzed prothrombin activation. Based on these results, we conclude that we have purified from bovine aortic intima an anticoagulant protein, which exerts its activity through a calcium-dependent binding to negatively charged phospholipids, and thus interferes with the assembly of prothrombinase on the phospholipid surface.The enzymes active in the process of blood coagulation belong to the class of serine proteases, and circulate in the blood as nonenzymatic precursors, the zymogens [l -31. The activation of such a zymogen proceeds in a proteolytic process in which an already activated coagulation factor cleaves a specific bond of its substrate, a zymogen [4]. The rate of this reaction is extremely low, but can be greatly enhanced by the presence of certain nonenzymatic cofactors, which can be divided into protein cofactors and negatively charged surfaces. The factor-X,-catalyzed activation of prothrombin, for Correspondence to C. P. M. Reutelingsperger, Laboratorium voor Biochemie, Rijksuniversiteit Limburg, Postbus 616, NL-6200-MD Maastricht, The Netherlands Abbreviations. MPT test, modified prothombin time test; PhCOIle-Glu-Pip-Gly-Arg-NH-Np . HCI (S2337), N-benzoyl-~-isoleucyI-~-glutamyl-L-piperidyl-glycyl-L-arginine p-nitroanilide hydrochloride; DPhe-Pip-Arg-NH-Np . 2 HCI (S2238), ~-phenylakanyl-L-pipecolyI-L-arginine p-nitroanilide dihydrochloride; NaCl/Tris/HCl, 100 mM NaCI, 50 mM Tris/HCI, pH 7.5; NaCl/Tris/HCi/EDTA, NaCI/Tris/ HCI with 2 mM EDTA; NaCl/Tris/HCl/albumin, NaCl/Tris/HCl with 0.5 mg/ml human serum albumin, pH 7.9; RVV-X, purified factor X activator from Russell's viper venom; Gla, 4-carboxyglutamic acid; Ole2Gro-P-Cho, 1,2-dioleoyl-sn-glycero-3-phosphocholine; Ole2Gro-P-Ser, 1,2-dioleoyl-sn-glycero-3-ph...

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“…In recent years, it has become clear that the presence of LA is a risk factor for thrombosis [12,13], for recurrent spontaneous abortion [14], for thrombocytopenia, and for a variety of neurological disorders. LA are immunoglobulins that interfere with a variety of coagulation assays, prolonging phospholipiddependent coagulation [15][16][17]. We measured the plasma levels of FVIIa in three groups of subjects, patients positive and negative for LA, and healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Plasma-activated factor VII level in patients positive for lupus anticoagulant

et al. 1997

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We examined plasma levels of activated factor VII (F VIIa) in 50 patients positive for lupus anticoagulant (LA), in 83 patients negative for LA, and in 10 healthy volunteers as controls. Plasma F VIIa was present in healthy volunteers; its level was significantly increased, compared to the level in the controls, in patients with thrombosis, collagen diseases, and disseminated intravascular coagulation (DIC), suggesting that it reflected a thrombotic state. Plasma F VIIa was correlated with thrombin-antithrombin complex (TAT) in patients negative for LA but showed no such correlation in those positive for LA. Plasma F VIIa was negatively correlated with activated partial thromboplastin time (APTT) in patients positive for LA, but not in those negative for LA, suggesting that LA could inhibit the F VIIa assay system. Plasma F VIIa level was significantly increased in patients with thrombotic diseases; however, in patients positive for LA, it is possible that increased plasma F VIIa level may not be correlated with thrombogenicity. Am.

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Monoclonal immunoglobulin M lambda coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant.

Cited by 377 publications

References 44 publications

β₂‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

β₂‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

Purification and characterization of a novel protein from bovine aorta that inhibits coagulation

Plasma-activated factor VII level in patients positive for lupus anticoagulant

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Monoclonal immunoglobulin M lambda coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant.

Cited by 377 publications

References 44 publications

β2‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

β2‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

Purification and characterization of a novel protein from bovine aorta that inhibits coagulation

Plasma-activated factor VII level in patients positive for lupus anticoagulant

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Product

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β₂‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

β₂‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome