Abstract: Antiphospholipid syndrome (APS) is an adquired autoimmune pro-thrombotic disease characterized by arterial and/or venous thrombosis and/or fetal losses associated with the persistent presence of antiphospholipid antibodies (aPL) detectable by solid phase assays (anticardiolipin (aCL) and anti-β2 glycoprotein I, β2GPI) and/or functional coagulation test (lupus anticoagulant (LA)). Most patients with typical APS manifestations have the presence of one or more of conventional aPL, but, some patients might exhibit clinical features related with APS but with persistent negative determinations of “classic” aPL (seronegative APS). Expanding the network of autoantibodies in patients highly suspected of having APS but who have normal results from a conventional test using new antibodies (i.e., phosphatidylserine/prothrombin and β2GPI domain 1) would increase the diagnosis. Thrombosis is one of the leading causes of death among patients with cancer, representing up to 15% of all deaths. Cancer increases the risk of thrombosis and chemotherapy is further associated with a higher risk of thrombosis. In addition, aPL may contribute to an increased risk of thrombosis in patients with malignancies, although the levels do not seem to reflect their pathogenicity. Several malignancies, particularly hematological and lymphoproliferative malignancies, may indeed be associated with the generation of aPL but do not necessarily enhance the thrombophilic risk in these patients.
Abstract: Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thromboses and pregnancy morbidity associated with antiphospholipid antibodies: lupus anticoagulant, IgG or IgM anticardiolipin or anti-beta 2-glycoprotein I. The kidney is one of the major target organs in antiphospholipid syndrome (APS). However, beyond the known involvement of the kidney in primary and associated APS, we may be observing a new form of APS within the context of renal failure. This review describes the classical kidney manifestations of APS and provides new considerations to be taken into account.
Abstract: Antiphospholipid syndrome (APS) is a thrombophilic disorder that classically presents with vascular thrombosis and/or obstetric complications. APS is associated with antiphospholipid antibodies: a heterogeneous group of autoantibodies that are directed against membrane phospholipids in complex with phospholipid-binding proteins. Beta-2-glycoprotein I (B2GPI) binds anionic phospholipids and is considered to be the predominant antigen in APS and antibodies against B2GPI (anti-B2GPI) are recognised in the laboratory criteria for APS diagnosis. This review focuses on the part played by anti-B2GPI in the pathogenesis of APS, their associations with different clinical phenotypes of the disorder and new avenues for refining the diagnostic potential of anti-B2GPI testing.
Abstract: Antiphospholipid antibodies (aPL) are a hallmark of the antiphospholipid syndrome (APS), which is the most commonly acquired thrombophilia. To date there is consensus that aPL cause the clinical manifestations of this potentially devastating disorder. However, there is good evidence that not all aPL are pathogenic. For instance, aPL associated with syphilis show no association with the manifestations of APS. While there has been intensive research on the pathogenetic role of aPL, comparably little is known about the origin and development of aPL. This review will summarize the current knowledge and understanding of the origin and development of aPL derived from animal and human studies.
Abstract: The threshold between low and medium antibody levels for anticardiolipin (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) for the diagnosis of antiphospholipid syndrome (APS) remains a matter of discussion. Our goal was to create a protocol for determining the low/medium antibody cut-off for aCL antibody methods based on a clinical approach, and utilize it to establish the clinically-relevant low/medium threshold for QUANTA Flash aCL chemiluminescent immunoassay (CIA) results. The study included 288 samples from patients with primary APS (n = 70), secondary APS (n = 42), suspected APS (n = 36), systemic lupus erythematosus (SLE) without APS (n = 96) and other connective tissue diseases (n = 44). All samples were tested for IgG and IgM aCL antibodies with QUANTA Flash CIA, along with traditional enzyme-linked immunosorbent assays (ELISAs) (QUANTA Lite). The assay specific low/medium threshold for QUANTA Flash aCL IgG and IgM assays (i.e., the equivalent of 40 GPL and MPL units) was established as 95 and 31 chemiluminescent units (CU), respectively, based on clinical performance and comparison to QUANTA Lite ELISAs. Agreement between CIA and ELISA assay results improved substantially when the platform-specific low/medium antibody threshold was used, as compared to agreement obtained on results generated with the assay cutoff: Cohen’s kappa increased from 0.85 to 0.91 for IgG aCL, and from 0.59 to 0.75 for IgM aCL results. This study describes a clinical approach for establishing the low/medium antibody threshold for aPL antibody assays, and successfully employs it to define 95 and 31 CU, respectively, as the low/medium cut point for QUANTA Flash aCL IgG and IgM results. This study can serve as a model for labs wishing to establish the appropriate low/medium aPL antibody threshold when implementing new aPL antibody assays.
Abstract: Human immunoglobulin G (IgG) binding with zinc ions was examined using zinc ions immobilized on chelating Sepharose beads (Zn-beads). Human IgG bound to Zn-beads but not to Sepharose beads (control beads). Mouse, rat, bovine and equine IgGs also bound to Zn-beads, similar to human IgG. The human IgG F(c) fragment showed zinc ion–binding activity whereas the Fab fragment did not. Ethylenediaminetetraacetic acid (EDTA)-treated Zn-beads no longer bound human IgG; however, washing the beads, followed by the addition of zinc ions, restored the binding activity towards human IgG. Zn-beads saturated with human fibrinogen could bind human IgG, and Zn-beads saturated with human IgG could bind fibrinogen. These results suggest that animal IgGs, including human, specifically bind zinc ions, probably through a zinc-binding site in the F(c) fragment and not in the Fab fragment. In addition, IgG and fibrinogen interact with each other and/or bind zinc ions through different mechanisms.