Accuracy of Anticardiolipin Antibodies in Identifying a History of Thrombosis Among Patients With Systemic Lupus Erythematosus

doi:10.1016/S0002-9343(99)80014-X

The American Journal of Medicine

Volume 98, Issue 6, June 1995, Pages 559-565

https://doi.org/10.1016/S0002-9343(99)80014-X Get rights and content

objective

To measure the accuracy of anticardiolipin antibodies (aCL) in identifying a history of thrombosis among patients with systemic lupus erythematosus (SLE) or the primary antiphospholipid syndrome (PAPS).

patients and methods

Patients with SLE or PAPS who attended our rheumatology clinic between April 1992 and March 1994 were included in a retrospective analysis of the relationship between thrombotic events and aCL. All aCL measurements were performed in the same laboratory by enzyme-linked immunosorbent assay, blinded as to the presence or absence of thrombosis. The diagnostic accuracy of IgG, IgM, and IgA aCL was quantified by means of the receiver operating characteristic area under the curve (ROC AUC) for each isotype. Stratum-specific likelihood ratios and their 95% confidence intervals were calculated to define strata with optimal discriminant power. results: During the period of study, aCL was measured in 117 patients (113 SLE and 4 PAPS), of whom 24 (20.5%) had experienced thrombotic events. The ROC AUC ± the standard error for IgG aCL was 0.81 ± 0.05, signifying an 81% accuracy in the identification of a history of thrombosis. In contrast, the accuracy of the IgM and IgA aCL was significantly lower (0.60 ± 0.08 and 0.54 ± 0.07, respectively, P < 0.05). Using stratumspecific likelihood ratios, we defined three strata in the IgG aCL scale that discriminate between patients with low, indeterminate, and high probabilities of thrombosis. For IgG aCL levels below 21.4 IgG phospholipid (GPL) U/mL, the posttest probability of thrombosis was 0.07, whereas for IgG aCL levels ≥65.1 GPL U/mL, the posttest probability of thrombosis was 0.75. For IgG aCL values between 21.4 and 65.0 GPL U/mL, the probability of thrombosis was 0.20, equivalent to the entire cohort.

conclusions

The IgG aCL determinations perform well in the identification of thrombosis in SLE or PAPS, while the IgM and IgA aCL have poor diagnostic accuracy. These findings may have implications for management of these patients.

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Cited by (96)

Added value of antiphosphatidylserine/prothrombin antibodies in the workup of thrombotic antiphospholipid syndrome: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies
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Diagnosis of antiphospholipid syndrome (APS) requires persistent presence of lupus anticoagulant (LAC), anticardiolipin (aCL) IgG/IgM, or anti‐β2 glycoprotein I (aβ2GPI) IgG/IgM antibodies. Other antiphospholipid antibodies (aPL) such as antiphosphatidylserine/prothrombin antibodies (aPS/PT) are promising in assessment of thrombotic APS (TAPS).
To evaluate the added value of aPS/PT IgG and IgM in TAPS.
aPS/PT IgG/IgM, aCL IgG/IgM, aβ2GPI IgG/IgM, and LAC were determined in 757 patients (TAPS and controls). aPS/PT cut‐off values were calculated, and aPS/PT titers and positivity were compared between TAPS and controls, type of thrombosis, and antibody profiles. Likelihood ratios (LR), odds ratios (OR), and aPL score were determined.
aPS/PT IgG and IgM were associated with TAPS and triple positivity. In‐house calculated cut‐offs were higher for IgM (43 units), compared to manufacturer’s cut‐off (30 units). Thresholds of 90 (IgG) and 200 (IgM) units were determined as high‐titer cut‐off. Higher aPS/PT titers were observed in triple positive patients and showed higher LR and OR for TAPS. aPS/PT was independently associated with TAPS when adjusted for aCL/aβ2GPI, but not when adjusted for LAC. In isolated LAC positive patients, aPS/PT was positive in 27.1% TAPS patients and in 77.3% patients with autoimmune disease. Diagnostic value of aPL score did not differ with and without including aPS/PT.
aPS/PT positivity, especially with high antibody titer, is associated with TAPS diagnosis. Analysis on top of current laboratory criteria is not essential in TAPS diagnosis, but aPS/PT could be useful in patients with thrombosis and a double positive aPL profile (aCL+/aβ2GPI+).
The clinical relevance of IgA anticardiolipin and IgA anti-β2 glycoprotein I antiphospholipid antibodies. A systematic review.
2013, Autoimmunity Reviews
The antiphospholipid syndrome (APS) is diagnosed in patients with thromboembolic events and/or pregnancy loss in the presence of persistent laboratory evidence for antiphospholipid antibodies (aPL). Diagnostic tests for the detection of antiphospholipid antibodies include laboratory assays that detect anticardiolipin antibodies, lupus anticoagulants, and anti-β(2)-glycoprotein I antibodies. Most studies on aPL have mainly focused on the estimation of the IgG and IgM isotypes, with only a few studies reporting on the pathogenic significance of IgA aPL.
In this review we aimed to summarize and analyze the evidence published in the literature on the prevalence and the clinical significance of IgA aPL.
Antiphospholipid antibody profiling - Time for a new technical approach?
2012, Autoimmunity Reviews
Detection of anti-phospholipid (aPL) antibodies for state-of-the art diagnosis of antiphospholipid syndrome(APS) still remains a laboratory challenge due to the great diversity of aPL antibodies and their relevance with regard to the diagnostic criteria. According to the recently revised classification criteria for APS, several enzyme-linked immunosorbent assays (ELISAs) should be performed simultaneously in routine laboratories for the detection of aPL antibodies. Therefore, new approaches to aPL profiling have been proposed recently to provide information regarding diagnosis and eventually outcome in APS patients. Multiplex analysis could meet the increasing demand for cost-efficient detection and profiling of aPL antibodies. Multi-line immunodot assays or bead-based multiplex techniques candidate as alternatives to assess several aPL antibodies simultaneously employing different solid-phases for bound/free separation of reactants. Particularly, multi-line immunodot assays present an alternative to ELISA for aPL antibody detection and profiling in APS patients. The use of hydrophobic membranes as solid-surface by this technique appears to offer a distinct solid-phase reaction environment for the assessment of aPL antibodies. This article reviews novel developments in the field of laboratory diagnostics of APS with special emphasis on multiplex assays.
Chapter 3 Laboratory Heterogeneity of Antiphospholipid Antibodies
2009, Handbook of Systemic Autoimmune Diseases
Citation Excerpt :
In addition, the IgG isotype appears to be more closely associated with clinical manifestations than either the IgM or IgA isotypes (Harris et al., 1986; Gharavi et al., 1987; Escalante et al., 1995; Silver et al., 1996; Levine et al., 1997). Studies by Levine and Escalante and their respective colleagues demonstrated that medium and high levels of aCL antibodies are more significantly correlated with the clinical manifestations of APS (Escalante et al., 1995; Levine et al., 1997). According to Escalante et al., IgG aCL levels below 21.4 had a low (0.07) probability of thrombosis, while IgG aCL levels between 21.4 and 65.0 GPL had an increased probability of thrombosis of 0.20, and when aCL IgG values were greater than 65 GPL units they were associated with an even higher probability value of 0.75 (Escalante et al., 1995).
The anticardiolipin (aCL) test has been widely utilized by physicians since the mid-1980s for diagnosing patients with the antiphospholipid syndrome (APS). Establishment of this diagnosis has improved the management of patients with recurrent thrombosis and recurrent pregnancy losses. The test was first established in 1983 as a radioimmunoassay and soon thereafter converted into an enzyme-linked immunosorbent assay (ELISA). The other test commonly used in the diagnosis of APS is the lupus anticoagulant test (LAC). The aCL ELISA is sensitive for the diagnosis of APS but lacks specificity. On the other hand, the LAC assay, although more specific is not as sensitive as the aCL ELISA. More specific tests are now available such as the anti-β₂ glycoprotein I (anti-β2GPI) assay, the antiprothrombin (anti-PT) assay and other ELISAs that utilize negatively charged phospholipids other than cardiolipin to coat the plates. In the past 25 years, there have been numerous efforts to standardize aCL, LAC, and anti-β₂GPI tests. However, there are still reports of significant intra- and inter-laboratory variation in results for all three assays. This chapter discusses in detail the clinical utilities of these tests, technical problems associated with their use, the current laboratory classification criteria for diagnosis of APS, and possible new and better assays that may be available in the near future for diagnosis of APS.
CNS lupus: A study of 41 patients
2007, Neurology
CNS lupus is a serious but potentially treatable illness, which, though long recognized, may still present very difficult diagnostic challenges. We believed that further detailed study of patients with neuropsychiatric lupus would yield clinical information of practical value in improving both recognition and management of this difficult illness.
A retrospective case analysis of 41 patients with CNS systemic lupus erythematosus (CNS-SLE) was performed largely in the southwest of England and South Wales, covering the period 1990 to 2002.
We found that primary neurologic presentation of SLE was not rare (10/41 patients), and there was an unexpected emergence of movement disorders (particularly parkinsonism and myoclonus) early in the disease course (4/10 patients). These showed a good response to immunosuppressants, but not to standard dopaminergic therapy. Typically, the erythrocyte sedimentation rate (ESR) or plasma viscosity was elevated during neurologic episodes while C-reactive protein levels were normal, and lupus-related serum antibody tests usually supportive. But, significantly, neither a normal ESR nor negative serology excluded CNS lupus. MR brain imaging is more commonly abnormal in patients with focal neurologic deficits and normal or shows wholly nonspecific change with more diffuse manifestations (cognitive decline, epilepsy). Abnormal CSF correlated significantly with poorer outcome. At the end of the period of study, 54% had no more than minor functional disability, the remainder having a severe or fatal outcome.
Our observations, particularly the emergence of non-choreic movement disorders, the blood, serum, and imaging findings, and the prognostic importance of CSF abnormalities, should help improve both the recognition of CNS systemic lupus erythematosus, perhaps particularly in elderly individuals, and its management.
Response to: Correspondence on 'ACR/EULAR antiphospholipid syndrome classification criteria' by Damoiseaux and van Beers
2023, Annals of the Rheumatic Diseases

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Accuracy of Anticardiolipin Antibodies in Identifying a History of Thrombosis Among Patients With Systemic Lupus Erythematosus

objective

patients and methods

conclusions

Lancet.

Am J Med.

Am J Med.

Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986

Clin Exp Immunol.

The second international anti-cardiolipin standardization workshop/ the Kingston anti-phospholipid antibody study (KAPS) group

Am J Clin Pathol.

Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus and related disorders

Ann Intern Med.

Thrombosis, recurrent fetal loss and thrombocytopenia. Predictive value of the anticardiolipin antibody test

Arch Intern Med.

Measurement of anti-cardiolipin antibodies by an enzyme-linked immunosorbent assay (ELISA): standardization and quantitation of results