Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: Untangling the knot
21 Sep 2021-Journal of Thrombosis and Haemostasis (John Wiley & Sons, Ltd)-Vol. 19, Iss: 12, pp 3018-3030
TL;DR: In this paper, the authors compared the triple positivity of antiphospholipid antibodies (aPL) and single aCL-positive patients and found that the thrombotic risk does not necessarily increase with the number of positive tests.
About: This article is published in Journal of Thrombosis and Haemostasis.The article was published on 2021-09-21. It has received 3 citations till now. The article focuses on the topics: Lupus anticoagulant & Antiphospholipid syndrome.
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TL;DR:
Abstract: Diagnosis of antiphospholipid syndrome (APS) requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL). Currently, laboratory criteria aPL consist of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, and anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM. Diagnosis and risk stratification of APS are complex and efforts to standardize and optimize laboratory tests have been ongoing since the initial description of the syndrome. LAC detection is based on functional coagulation assays, while aCL and aβ2GPI are measured with immunological solid-phase assays. LAC assays are especially prone to interference by anticoagulation therapy, but strategies to circumvent this interference are promising. Alternative techniques such as thrombin generation for LAC detection and to estimate LAC pathogenicity have been suggested, but are not applicable yet in routine setting. For aCL and aβ2GPI, a lot of different assays and detection techniques such as enzyme-linked immunosorbent and chemiluminescent assays are available. Furthermore, a lack of universal calibrators or standards results in high variability between the different solid-phase assays. Other non-criteria aPL such as anti-domain I β2 glycoprotein I and antiphosphatidylserine/prothrombin antibodies have been suggested for risk stratification purposes in APS, while their added value to diagnostic criteria seems limited. In this review, we will describe laboratory assays for diagnostic and risk evaluation in APS, integrating applicable guidelines and classification criteria. Current insights and hindrances are addressed with respect to both laboratory and clinical implications.
7 citations
TL;DR: Since IFN-I expression was not increased in aPL carriers or associated with a higher-risk aPL profile, this mechanism does not appear to be related to the presence of aPL alone.
Abstract: Background: Thrombotic risk in antiphospholipid syndrome (APS) is conferred by the association of antiphospholipid (aPL) antibodies (first hit) with additional pro-coagulant stimulus (second hit), such as inflammation. Among inflammatory responses, the production of large amounts of interferon (IFN)-I by plasmacytoid dendritic cells (pDCs) is at the basis of the pathophysiology of systemic autoimmune disorders, which raises the hypothesis that this mechanism could also be associated with vascular manifestations of APS. Purpose: Here, we determined the association of pDCs and IFN-I production with thrombotic APS. Research design: Patients with thrombotic primary (t-PAPS) and secondary APS (t-SAPS), asymptomatic aPL carriers and individuals without thrombosis (controls) were included. Data collection and analysis: Circulating pDCs and IFN-α intracellular expression (in the presence or not of oligodeoxynucleotides (CP) stimulus) were quantified by flow cytometry. The expression of five IFN-I inducing genes: ISG15, OASL, Ly6E, MX1, and OAS1 in mononuclear cells was determined by qPCR. Between-group differences were evaluated using chi-square or Kruskal–Wallis tests. Results: A total of 50 patients with t-PAPS, 50 patients with t-SAPS, 20 aPL carriers, and 50 individuals without thrombosis (controls) were included. Intracellular expression of IFN-α was increased after CPG stimulation in both t-SAPS (1.56%; IQR 1.07–2.02) and t-PAPS (0.96%; IQR 0.55–1.24), when compared to aPL carriers (0.71%; IQR 0.42–0.93) and controls (0.48%; IQR 0.24–0.78; p < .0001). ISG15, OASL, Ly6E, MX1, and OAS1 mRNA expressions were higher in t-SAPS (but not in t-PAPS) than in aPL carriers and controls. The expression of proteins and mRNA related to IFN-I response was similar between the triple aPL-positive profile and other aPL profiles. Conclusion: Our results indicate an association of IFN-I response and t-APS. Since IFN-I expression was not increased in aPL carriers or associated with a higher-risk aPL profile, this mechanism does not appear to be related to the presence of aPL alone. IFN-I response could possibly constitute a complementary mechanism for triggering clinical manifestations in APS.
2 citations
TL;DR: In this article , the authors analyzed the antiphospholipid antibody persistence over time in patients with APS and its association with clinical recurrence and to identify predictors of aPL persistence.
1 citations
References
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University of New South Wales1, Hospital for Special Surgery2, Hokkaido University3, University of Utah4, University of Texas Health Science Center at San Antonio5, Utrecht University6, University of Milan7, Geneva College8, Sheba Medical Center9, University of Brescia10, National and Kapodistrian University of Athens11
TL;DR: This document appraise the existing evidence on clinical and laboratory features of APS addressed during the forum and proposes amendments to the Sapporo criteria, including definitions on features ofAPS that were not included in the updated criteria.
5,699 citations
TL;DR: Modalities for blood collection and processing are fully delineated and the choice of tests is limited to dRVVT and a sensitive aPTT and the interpretation of the results in general and in particular situations is reported.
1,068 citations
TL;DR: The antiphospholipid syndrome is a prothrombotic disorder associated with autoantibodies associated with obstetrical complications as well as venous and arterial thrombosis risks.
Abstract: The antiphospholipid syndrome is a prothrombotic disorder associated with autoantibodies. It is associated with obstetrical complications (mainly spontaneous abortion) as well as venous and arterial thrombotic risks. Insights into disease mechanisms have led to new therapies.
571 citations
TL;DR: Characterization of the molecular basis of the pathogenic mechanisms involved, including the putative second hits and the role of complement activation, might offer an answer to this question.
Abstract: Antiphospholipid antibodies (aPL) are both diagnostic markers for, and pathogenic drivers of, antiphospholipid syndrome (APS). Although the presence of aPL is a necessary pre-condition, APS-associated clotting is seemingly triggered by an additional 'second hit', frequently related to innate inflammatory immune responses. β(2) glycoprotein I (β(2)GPI)-dependent aPL, the most important subset of these antibodies, mediate several--not necessarily alternative--thrombogenic mechanisms, mainly on the basis of their reactivity with β(2)GPI expressed on the membrane of cells that participate in the coagulation cascade. Recurrent pregnancy complications associated with aPL cannot be explained solely by thrombosis, and alternative pathogenic mechanisms have been reported. Although one in vivo model of fetal loss suggests a mechanism of aPL-mediated acute placental inflammation, other models and the histopathological examination of APS placentae do not support a widespread inflammatory signature. β(2)GPI-dependent aPL are thought to recognize their antigen on placental tissues, inhibit the growth and differentiation of trophoblasts, and eventually cause defective placentation. Why antibodies with similar antigen specificity produce different clinical manifestations is not clear. Characterization of the molecular basis of the pathogenic mechanisms involved, including the putative second hits and the role of complement activation, might offer an answer to this question.
497 citations
TL;DR: A recent systematic review of the literature showed lupus anticoagulants to be risk factors of thrombosis, independent of the type and site of the event, the presence of antiphospholipid antibodies.
405 citations