Acquired Inhibitors in Nonhemophilic Patients

Lechner, Klaus

doi:10.1159/000214043

Cited by 74 publications

(73 citation statements)

References 50 publications

(111 reference statements)

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“…Consistent an IgM paraprotein with specificity against phosphoryl-)ns, high specific radioactivity choline has also been described (29). No (2)(3)(4)(5).…”

Section: Resultsmentioning

confidence: 74%

“…espite the abnormalities in co-Our current concept is that negatively charged phostimes of a marked degree, the pholipid micelles function as a surface upon which Lnticoagulant, per se, is seldom both the activation of Factor X by Factor IXa in the eding tendency (1)(2)(3)(4)(5). In fact, presence of Factor VIII and the activation of proreported in at least 13 patients thrombin by Factor Xa in the presence of Factor V ants (20)(21)(22), one of whom has can occur.…”

Section: Resultsmentioning

confidence: 99%

“…scribed in a variety of diseases (2)(3)(4)(5). The presence of such an inhibitor, to which the term "lupus anticoagulant" has been applied, is characterized by the impaired conversion of prothrombin to thrombin, most frequently reflected in the prolongation of prothrombin and partial thromboplastin times.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of such an inhibitor, to which the term "lupus anticoagulant" has been applied, is characterized by the impaired conversion of prothrombin to thrombin, most frequently reflected in the prolongation of prothrombin and partial thromboplastin times. The immunoglobuliin nature of these anticoagulants has been demonstrated but their precise mechanism of action has not been delineated (2)(3)(4)(5). Individuals with lupus anticoagulants rarely have deficiency of only a single coagulation factor, although hypoprothrombinemia has been reported occasionally (3), and no specific coagulation factor inhibition has been demonstrated for such anticoagulants.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Thiagarajan¹,

Shapiro²,

Marco³

1980

J. Clin. Invest.

376

137

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“…Consistent an IgM paraprotein with specificity against phosphoryl-)ns, high specific radioactivity choline has also been described (29). No (2)(3)(4)(5).…”

Section: Resultsmentioning

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Thiagarajan¹,

Shapiro²,

Marco³

1980

J. Clin. Invest.

376

137

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“…Immunology: Rauch and Janoff phospholipid portion of the prothrombin activator complex provided by the exogenously added brain cephalin in the assay system (17)(18)(19)(20)(21)(22). We measured APTTs in platelet-poor plasma drawn from each immunized mouse.…”

mentioning

confidence: 99%

Phospholipid in the hexagonal II phase is immunogenic: evidence for immunorecognition of nonbilayer lipid phases in vivo.

Rauch

Janoff

1990

Proc. Natl. Acad. Sci. U.S.A.

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Immunization of mice with phosphatidylethanolamine in the hexagonal II phase but not the biayer phase resulted in the induction ofanti-phospholipid antibodies. These antibodies, which were strongly reactive with phosphatidylethanolamine and crossreactive with cardiolipin, had functional lupus anticoagulant activity and were characteristic of autoantibodies common in patients with autoimmune disease. Recognition of the hexagonal II phase by the afferent limb of the immune system suggests that nonbilayer phospholipids can arise in the course of membrane remodeling and induce the autoantibodies of disease.Antibodies to phospholipids are associated with a variety of autoimmune diseases, including systemic lupus erythematosus and related rheumatic disorders (1-3). The mechanisms responsible for the production of these autoantibodies have not been elucidated. Although phospholipids have long been considered to be nonimmunogenic, only bilayer phase phospholipids have been studied (reviewed in refs. 4 and 5). Our findings that lupus anticoagulants (a subset of anti-phospholipid antibodies associated with thrombosis, thrombocytopenia, and multiple spontaneous abortions) recognize nonbilayer phase (hexagonal II) but not bilayer phase phosphatidylethanolamine (6-11) led us to ask whether the lipid polymorphic phase could modulate immunogenicity. Here we show that hexagonal II phase, but not bilayer phase, phosphatidylethanolamine is capable of inducing antiphospholipid antibodies with lupus anticoagulant activity in mice. Hexagonal II phase lipid, as opposed to the familiar bilayer phase lipid, consists of hexagonally packed cylinders of lipid where the cylinders are composed of a central aqueous channel toward which the polar groups are oriented. The studies reported here thus demonstrate that phospholipid can be immunogenic and suggest that alterations in lipid phase in vivo may lead to the production ofanti-phospholipid antibodies with associated pathological sequelae. MATERIALS AND METHODSPhospholipids. All phospholipids were purchased from Avanti Polar Lipids and used without further purification. Phospholipid suspensions were prepared in Hepes buffer (20 mM Hepes/150 mM NaCl, pH 7.5) as described (6).Immunizations. Three-month-old female BALB/c mice (The Jackson Laboratory) were bled for preimmune sera and immunized intravenously with equimolar (0.02 ,umol per 100Al of injection) amounts of phospholipid diluted in saline, as determined by the method of Bartlett (12). Mice were given four injections at 2-week intervals and bled 12 days after the fourth injection.ELISAs. ELISAs were performed as described (13), with the following modifications. Phospholipid-coated plates were blocked with 0.01 M phosphate-buffered saline at pH 7.3 (PBS) containing 0.3% gelatin and 10% (vol/vol) fetal bovine serum for 2 hr at 250C. Sera were diluted 1:100 in PBS containing 0.3% gelatin and incubated for 3 hr at 250C. Alkaline phosphatase-conjugated goat anti-mouse immunoglobulin (polyvalent, Sigma) was incubated for 16 hr at 40C...

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The anticardiolipin syndrome. A new way to slice an old pie, or a new pie to slice?

Sontheimer¹

1987

Archives of Dermatology

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Acquired Inhibitors in Nonhemophilic Patients

Cited by 74 publications

References 50 publications

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

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

Phospholipid in the hexagonal II phase is immunogenic: evidence for immunorecognition of nonbilayer lipid phases in vivo.

The anticardiolipin syndrome. A new way to slice an old pie, or a new pie to slice?

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