Prevalence, persistence and clinical correlations of classic and novel antiphospholipid antibodies in systemic lupus erythematosus

Marchetti, Tess; Ribi, Camillo; Perneger, Thomas; Trendelenburg, Marten; Huynh‐Do, Uyen; Moerloose, Philippe de; Chizzolini, Carlo

doi:10.1093/rheumatology/key095

Cited by 25 publications

(19 citation statements)

References 42 publications

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“…This emphasizes the potential pathogenicity of IgG aPS/PT antibodies. These data are in accordance with recently published study (40) which postulates the pathogenicity of the aPS/PT antibodies of IgG and not of IgM isotype in patients with APS secondary to lupus.…”

Section: Discussionsupporting

confidence: 93%

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Prevalence and Significance of Non-conventional Antiphospholipid Antibodies in Patients With Clinical APS Criteria

et al. 2018

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Background: The biological diagnostics of antiphospholipid syndrome (APS) takes into account the persistent positivity for anticardiolipin and/or anti-β2GP1 antibodies and/or presence of lupus anticoagulant (LA). However, some non-conventional antiphospholipid antibodies have emerged that could help in the diagnosis of APS.Objectives: To study the potential usefulness of non-conventional antiphospholipid antibodies in clinical practice.Methods: Eighty-seven patients, aged from 15 to 92 years were included and classified in following groups: 41 patients positive for the conventional antibodies with clinical criterion of APS (31 with primary APS and 10 secondary), 17 seronegative APS (SNAPS) patients (i.e., persistent negativity for the conventional antibodies with a strong clinical suspicion of APS), 11 asymptomatic antiphospholipid antibodies carriers (i.e., persistent positivity for the conventional antibodies without clinical evidence of APS), and 18 patients presenting with a first thrombotic or obstetrical event. IgG and IgM were detected to the following antigens: phosphatidylserine/prothrombin (PS/PT) by ELISA, and phosphatidic acid, phosphatidyl-ethanolamine, phosphatidyl-glycerol, phosphatidyl-inositol, phosphatidylserine, annexin V, prothrombin by immunodot. Anti-β2GP1 IgA, and anti-β2GP1 domain 1 IgG were detected by chemiluminescence.Results: Positivity for the non-conventional antibodies was correlated with APS severity; patients with catastrophic APS (CAPS) being positive for 10.7 (Median, Range: 5–14) non-conventional antibodies. 9/17 seronegative patients were positive for at least one of non-conventional antibodies. A study of non-supervised hierarchical clustering of all markers revealed that anti-PS/PT antibodies showed high correlation with the presence of LA. All patients with APS triple positivity (highest risk profile) exhibited also persistent positivity for anti-PS/PT antibodies.Conclusions: Our data obtained from a prospective cohort constituted mainly by patients with primary APS, suggest that non-conventional APS antibodies may be useful for patients classified as SNAPS. They demonstrate the potential value of aPS/PT antibodies as a strong marker of APS. We propose that anti-PS/PT antibodies could be a surrogate APS biological marker of LA to classify in high-risk profile patients treated by direct oral anticoagulants (DOACs), in whom LA detection cannot be achieved.

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Section: Discussionsupporting

confidence: 93%

“…So, in these situations, aPS/PT antibodies (IgM and IgG) measuring could be considered to help to confirm or rule out the presence of LA (40).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Significance of Non-conventional Antiphospholipid Antibodies in Patients With Clinical APS Criteria

et al. 2018

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“…However, the term "seronegative APS" has been suggested to describe patients who have a clinical profile suggestive of APS but persistently test negative for aPLs by the conventional routine assays [31]. Several research groups have investigated novel methodological approaches to detect nontraditional aPLs, that is, different isotypes and/ or other autoantigens, in patients with clinically suspected seronegative APS [32][33][34]. It cannot be excluded that the case we here describe, who in addition to Libman-Sacks endocarditis experienced migraine and a deep vein thrombosis during her first pregnancy, actually had aPLs not detected by the current routine methodology.…”

Section: Discussionmentioning

confidence: 99%

Active NET formation in Libman–Sacks endocarditis without antiphospholipid antibodies: A dramatic onset of systemic lupus erythematosus

et al. 2018

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Although neutrophil extracellular traps (NETs) have been highlighted in several systemic inflammatory diseases, their clinical correlates and potential pathological role remain obscure. Herein, we describe a dramatic onset of systemic lupus erythematosus (SLE) with clear-cut pathogenic implications for neutrophils and NET formation in a young woman with cardiac (Libman-Sacks endocarditis) and central nervous system (psychosis and seizures) involvement. Despite extensive search, circulating antiphospholipid autoantibodies, a hallmark of Libman-Sacks endocarditis, could not be detected. Instead, we observed active NET formation in the tissue of the mitral valve, as well as in the circulation. Levels of NET remnants were significantly higher in serially obtained sera from the patient compared with sexmatched blood donors (p ¼ .0011), and showed a non-significant but substantial correlation with blood neutrophil counts (r ¼ 0.65, p ¼ .16). The specific neutrophil elastase activity measured in serum seemed to be modulated by the provided immunosuppressive treatment. In addition, we found anti-Ro60/SSA antibodies in the cerebrospinal fluid of the patient but not NET remnants or increased elastase activity. This case illustrates that different disease mechanisms mediated via autoantibodies can occur simultaneously in SLE. NET formation with release of cytotoxic NET remnants is a candidate player in the pathogenesis of this non-canonical form of Libman-Sacks endocarditis occurring in the absence of traditional antiphospholipid autoantibodies. The case description includes longitudinal results with clinical follow-up data and a discussion of the potential roles of NETs in SLE.

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“…The absorbance was reader to 280 nm, the peaks (containing IgG) were collected, concentrated and dialyzed against PBS buffer pH 7.4, and the fraction was maintained at −80 °C. The IgA and IgM data were not included since IgG is the one with the highest clinical correlation in APS [5].…”

Section: Methods Detailsmentioning

confidence: 99%

Methodology of generation and purification of anti-beta 2 glycoprotein I antibodies

et al. 2019

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Prevalence, persistence and clinical correlations of classic and novel antiphospholipid antibodies in systemic lupus erythematosus

Abstract: In this SLE cohort, the non-criteria aPL aD1 IgG and aPS-PT IgG performed differently. aD1 IgG was highly enriched in triple-positive samples, and aPS-PT IgG, jointly with LA, was associated with thrombotic events.

Cited by 25 publications

References 42 publications

Prevalence and Significance of Non-conventional Antiphospholipid Antibodies in Patients With Clinical APS Criteria

Prevalence and Significance of Non-conventional Antiphospholipid Antibodies in Patients With Clinical APS Criteria

Active NET formation in Libman–Sacks endocarditis without antiphospholipid antibodies: A dramatic onset of systemic lupus erythematosus

Methodology of generation and purification of anti-beta 2 glycoprotein I antibodies

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