Abstract
Background: Anti-phospholipid syndrome (APS) and systemic lupus erythematous (SLE) are autoimmune disorders that often co-occur. Anti-phospholipid antibodies (aPL) are typical of both conditions and may be associated with vascular events and pregnancy-related morbidities. Whereas, aPL-screening is mandatory for individuals with suspected SLE, the clinical value of longitudinal aPL analyses in established SLE is unclear.Methods: We investigated the occurrence and variation of IgG/IgA/IgM anti-cardiolipin (aCL) and anti-β2-glycoprotein-I (anti-β2GPI) antibodies, using both the manufacturer's cut-off and a cut-off based on the 99th percentile of 400 apparently healthy donors, in recent-onset SLE. Furthermore, we evaluated the relationships between aPL levels and SLE/APS manifestations, as well as the pharmacotherapy. Patients with SLE who met validated classification criteria were included in this prospective study (N = 54). Samples were obtained at 0, 6, 12, 24, 36, 48, 60, 72, 84, and 96 months after SLE diagnosis.Results: Depending on the cut-off applied, 61.1 or 44.4% showed a positive result for at least one aPL isotype or the lupus anticoagulant test over time. Median values for all six aPL isotypes numerically decreased from inclusion to last follow-up, but none of the isotypes met statistical significance. Seroconversion (from positive to negative, or the opposite direction) was occasionally seen for both aCL and anti-β2GPI. IgA and IgM anti-β2GPI were the most common isotypes, followed by IgM aCL. Presence of IgG aCL associated significantly with myocardial infarction and miscarriage, and IgG/IgA anti-β2GPI with miscarriage.Conclusion: aPL were common during the first years of SLE. Even though the levels fluctuated over time, the patients tended to remain aPL positive or negative. Repeated aPL testing in the absence of new symptoms seems to be of uncertain value in patients with recent-onset SLE.
Highlights
Antiphospholipid syndrome (APS) and systemic lupus erythematous (SLE) are distinct autoimmune disorders, they share several features and are often regarded as two sides of the same coin [1, 2]
The aPL levels fluctuated over time, the patients tended to remain aPL-positive or aPL-negative and the clinical value of repeated aPL-testing in the absence of thromboembolic events or new symptoms appears to be limited
We have previously reported that analyzing IgA aPL in addition to IgG and IgM in patients with SLE has limited clinical value [23]
Summary
Antiphospholipid syndrome (APS) and systemic lupus erythematous (SLE) are distinct autoimmune disorders, they share several features and are often regarded as two sides of the same coin [1, 2]. Antibodies directed against other proteins of the coagulation cascade, such as prothrombin and phosphatidylserine-prothrombin complexes, are examples of other aPL that are not (yet) included in APS classification criteria [1]. This is because they are not used routinely, or there is some uncertainty as to their clinical significance, or there is a lack of standardized testing. Some studies have shown that one of the five domains of β2GPI, domain I, is of particular importance for the pathogenesis of APS [9, 10] Antibodies directed against this specific domain appear to be strongly associated with thrombosis, as well as with obstetric complications, as compared to antibodies that target the entire β2GPI molecule [11]. Mean (range), years 44 [18–82]
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