Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome

Asherson, Ronald A.; Khamashta, Munther A.; Gil, Antonio; Vázquez, J. J.; Chan, Otto; Baguley, Elaine; Hughes, G. R. V.

doi:10.1016/0002-9343(89)90335-5

Cited by 318 publications

(119 citation statements)

References 49 publications

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“…Because the standardized assay for anticardiolipin antibodies, as described by the Anticardiolipin Wet Workshop report (28), recommends plating of cardiolipin by "evaporation of ethanol overnight at 4ЊC," a condition that would clearly lead to oxidation of the plated phospholipid, we hypothesized that some of the aPL were in fact directed to oxidized phospholipid epitopes. Furthermore, a growing body of evidence suggested a relationship of aPL not only to stroke (4,(46)(47)(48)(49), but to coronary artery disease as well (6,(50)(51)(52). The studies described in this report validated our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.

Hörkkö¹,

Miller²,

Dudl³

et al. 1996

J. Clin. Invest.

298

118

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The optimal clinical management of patients with antiphospholipid antibody syndrome (APS) is uncertain because of a lack of an underlying hypothesis to explain why antiphospholipid autoantibodies (aPL) form to such ubiquitous compounds as phospholipids (PL). In this paper, we demonstrate that many, if not most, aPL are actually directed at neoepitopes of oxidized PL, or neoepitopes generated by adduct formation between breakdown products of oxidized PL and associated proteins. Each cardiolipin (CL) molecule contains four unsaturated fatty acids and is highly susceptible to oxidation, particularly upon exposure to air. Yet, standard anticardiolipin antibodies (aCL) immunoassays routinely bind CL to microtiter wells by evaporation of the ethanol solvent overnight at 4 Њ C. Using a variety of techniques, we demonstrated that rapid oxidation occurs when CL is plated and exposed to air. Sera from apo E-deficient mice, which have high autoantibody titers to oxidized low density lipoprotein, showed a striking time-dependent increase in binding to CL that was exposed to air for increasing periods of time. Monoclonal antibodies to oxidized LDL, cloned from the apo E-deficient mice, also bound to oxidized CL. Both sera and affinity-purified aCL-IgG from APS patients bound to CL progressively as it was oxidized. However, the monoclonal antibodies from apo E-deficient mice, or sera or aCL-IgG from APS patients did not bind to a reduced CL analog that was unable to undergo peroxidation. These data demonstrate that many aPL are directed at neoepitopes of oxidized phospholipids, and suggest that oxidative events may be important in the pathophysiology of APS. In turn, this suggests new therapeutic strategies, possibly including intensive antioxidant therapy.

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Section: Discussionmentioning

confidence: 99%

Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.

Hörkkö¹,

Miller²,

Dudl³

et al. 1996

J. Clin. Invest.

298

118

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“…Patients with high titers of aPL are prone to a variety of thrombotic episodes and to fetal loss (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Antiphospholipid antibodies can be detected by lupus anticoagulant (LAC) assay or by enzyme immunoassays (EIA) against phospholipids.…”

mentioning

confidence: 99%

Antibodies to β₂‐glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus

Tsutsumi

Matsuura

Ichikawa

et al. 1996

Arthritis & Rheumatism

211

109

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Objective. To investigate whether anticardiolipin antibodies (aCL) in patients with systemic lupus erythematosus (SLE) bind to β2‐glycoprotein I (β2GPI), and to search for a relationship between the presence of IgG and/or IgM anti‐β2GPI antibody and clinical manifestations in SLE patients. Methods. IgG and IgM anti‐β2GPI in 308 Japanese SLE patients were measured using phospholipid‐independent enzyme immunoassays. Relationships to clinical histories and to various laboratory data were examined. Results. The values of anti‐β2GPI and aCL, as measured by conventional enzyme immunoassay, showed a strong correlation, but the anti‐β2GPI assay was more useful in distinguishing β2GPI‐dependent aCL from β2GPI‐independent aCL. The presence of IgG anti‐β2GPI was associated with an increased frequency of a history of thrombosis. Comparisons of various laboratory data suggested that the titer of anti‐β2GPI may fluctuate with disease activity. Conclusion. The results suggest that pathogenic aCL is directed against structurally altered β2GPI and that enzyme immunoassay for anti‐β2GPI may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE.

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“…The association of lupus anticoagulant (LAC) and/or anticardiolipin antibodies (aCL) with neurologic disorders, mainly focal cerebral and ocular ischemia, is well recognized in systemic lupus erythematoms (SLE) (1). However, there are less wellsubstantiated reports supporting an association between antiphospholipid antibodies (aPL) and other neurologic conditions such as migraine, lupoid sclerosis, Guillain-BarrC syndrome, or epilepsy.…”

mentioning

confidence: 99%

Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus

Herranz¹,

Rivier

Khamashta

et al. 1994

Arthritis & Rheumatism

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164

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Objective. To determine whether the occurrence of seizures is correlated with the presence of serum antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE) patients.Methods. The study included 221 unselected patients with SLE. Of these, 21 patients with epileptic seizures not attributed to any cause other than SLE were identified. Epilepsy was diagnosed by clinical history and electroencephalography. Blood samples were tested for the presence of antibodies to cardiolipin (aCL, IgG and IgM isotypes) and lupus anticoagulant (LAC).Results. LAC was detected in 43.8% of the patients with epilepsy and in 20.8% of controls (P = 0.057). A statistically significant association was found between moderate-to-high titers of IgG aCL and the presence of seizures (P = 0.02). Brain computed tomography and/or magnetic resonance imaging scanning was performed in 14 patients. All patients with abnormal features found on these tests had positive aPL (P = 0.03). Nine patients (42.9%) had at least 1 of the classic features associated with the aPL syndrome. Conclusion. We confirmed that epilepsy as a primary neuropsychiatric event is significantly associated with moderate-to-high titers of IgG aCL in SLE

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Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome

Cited by 318 publications

References 49 publications

Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.

Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.

Antibodies to β₂‐glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus

Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus

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Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome

Cited by 318 publications

References 49 publications

Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.

Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.

Antibodies to β2‐glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus

Association between antiphospholipid antibodies and epilepsy in patients with systemic lupus erythematosus

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Antibodies to β₂‐glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus