Livedoid vasculitis with anticardiolipin antibodies: improvement with danazol

SummaryMost anticardiolipin antibodies (ACA) associated with antiphospholipid syndrome (APS) are directed against epitopes expressed on β2-glycoprotein I (β2GPI). Despite a good correlation between standard ACA assays and those using purified human β2GPI as the sole antigen, some sera from APS patients only react in the latter. This is indicative of heterogeneity in anti-β2GPI antibodies. To characterize their reactivity profiles, human and bovine β2GPI were immobilized on γ-irradiated plates (β2GPI-ELISA), plain polystyrene precoated with increasing cardiolipin concentrations (CL/β2GPI-ELISA), and affinity columns. Fluid-phase inhibition experiments were also carried out with both proteins. Of 56 selected sera, restricted recognition of bovine or human β2GPI occurred respectively in 10/29 IgA-positive and 9/22 IgM-positive samples, and most of the latter (8/9) were missed by the standard ACA assay, as expected from a previous study. Based on species specificity and ACA results, IgG-positive samples (53/56) were categorized into three groups: antibodies reactive to bovine β2GPI only (group I) or to bovine and human β2GPI, group II being ACA-negative, and group III being ACA-positive. The most important group, group III (n = 33) was characterized by (i) binding when β2GPI was immobilized on γ-irradiated polystyrene or cardiolipin at sufficient concentration (regardless of β2GPI density, as assessed using 125I-β2GPI); (ii) and low avidity binding to fluid-phase β2GPI (Kd in the range 10–5 M). In contrast, all six group II samples showed (i) ability to bind human and bovine β2GPI immobilized on non-irradiated plates; (ii) concentration-dependent blockade of binding by cardiolipin, suggesting epitope location in the vicinity of the phospholipid binding site on native β2GPI; (iii) and relative avidities approximately 100-fold higher than in group III. Group I patients were heterogeneous with respect to CL/β2GPI-ELISA and ACA results (6/14 scored negative), possibly reflecting antibody differences in terms of avidity and epitope specificity. Affinity fractionation of 23 sera showed the existence, in individual patients, of various combinations of antibody subsets solely reactive to human or bovine β2GPI, together with cross-species reactive subsets present in all samples with dual reactivity namely groups III and II, although the latter antibodies were poorly purified on either column. Therefore, the mode of presentation of β2GPI greatly influences its recognition by anti-β2GPI antibodies with marked inter-individual heterogeneity, in relation to ACA quantitation and, possibly, disease presentation and pathogenesis.

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Relative Sensitivity of Different Tests in the Detection of Low Titer Lupus Anticoagulants

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647032 ◽

1988 ◽

Vol 60 (02) ◽

pp. 217-219 ◽

Cited By ~ 26

Author(s):

B Lesperance ◽

M David ◽

J Rauch ◽

C Infante-Rivard ◽

G E Rivard

Keyword(s):

Relative Sensitivity ◽

Fetal Outcome ◽

Anticardiolipin Antibodies ◽

Lupus Anticoagulants ◽

Normal Plasma ◽

Coagulation Tests ◽

High Dilutions ◽

Tissue Thromboplastin ◽

High Concentrations ◽

Kaolin Clotting Time

SummaryLupus anticoagulants (LA) and anticardiolipin antibodies have been strongly associated with recurrent abortion and fetal death. Because steroids have been reported to improve the fetal outcome of LA associated pregnancies, presumably by decreasing the levels of LA, it becomes desirable to have a simple and reliable test to monitor the levels of the putative antibody. To this effect, we assessed the capacity of the following coagulation tests to detect the presence of LA in serial dilutions of patient plasma with pooled normal plasma: kaolin clotting time (KCT), tissue thromboplastin inhibition test (TTIT), dilute Russell Viper venom time (DRVVT) and activated partial thromboplastin time with standard and high concentrations of phospholipids (SC and HCAPTT). All samples were also evaluated for the presence of anticardiolipin antibodies with an ELISA. The KCT was able to detect LA at a much greater dilution in normal plasma than any of the other clotting assays. The ELISA was comparable to KCT in its ability to detect high dilutions of LA.

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Anticardiolipin Antibodies Are Elevated in HIV-1 Infected Haemophiliacs but Do Not Predict for Disease Progression

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646531 ◽

1989 ◽

Vol 61 (01) ◽

pp. 081-085 ◽

Cited By ~ 22

Author(s):

Simon Panzer ◽

Christoph Stain ◽

Hubert Hartl ◽

Robert Dudczak ◽

Klaus Lechner

Keyword(s):

Normal Values ◽

Anticardiolipin Antibodies ◽

Haemophilia A ◽

Serum Samples ◽

Factor Viii Concentrates ◽

Patient Groups ◽

Anti Hiv ◽

Hiv 1 ◽

Cd4 Lymphocytes

SummaryLevels of anticardiolipin antibodies (ACA) were measured in 55 patients with haemophilia A in serum samples obtained in 1983 and in 1987. Twenty-one patients were negative for anti HIV-1 antibodies in 1983 and remained negative in 1987; 34 patients had anti HIV-1 antibodies in 1983; 17 of these latter patients remained asymptomatic, whereas 17 patients developed ARC or AIDS during the 4 years follow-up. Thirteen anti HIV-1 negative patients had elevated ACA levels in 1983; subsequently, a significant decrease was observed in all these subjects (p <0.001). All anti HIV-1 positive patients had elevated ACA levels in 1983; normal values were found in 9 patients in 1987. Yet, these changes were not significant (p >0.05). ACA levels were significantly higher in HIV-1 infected patients than in those without anti HIV-1 antibodies (p <0.05). There was no difference of ACA levels between the two anti HIV-1 positive patient groups, be it in 1983 or be it in 1987 (p >0.05). There was no correlation of ACA levels with serum IgG concentrations, CD4+ lymphocytes, or the consumption of factor VIII concentrates.

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The Relationship between Plasma Microparticles, Protein S and Anticardiolipin Antibodies in Patients with Human Immunodeficiency Virus Infection

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650519 ◽

1996 ◽

Vol 76 (01) ◽

pp. 038-045 ◽

Cited By ~ 24

Author(s):

Jean-Christophe Gris ◽

Pierre Toulon ◽

Sophie Brun ◽

Claude Maugard ◽

Christian Sarlat ◽

...

Keyword(s):

Poor Prognosis ◽

Anticardiolipin Antibody ◽

Protein S ◽

Anticardiolipin Antibodies ◽

Protein S Deficiency ◽

Free Protein ◽

Precipitation Technique ◽

S Deficiency ◽

Immunodeficiency Virus ◽

Antibody Titers

SummaryThe high prevalence of free protein S deficiency in human immunodeficiency virus (HlV)-infected patients is poorly understood. We studied 38 HIV seropositive patients. Free protein S antigen values assayed using the polyethylene-glycol precipitation technique (PEG-fS) were statistically lower in patients than in controls. These values using a specific monoclonal antibody-based ELISA (MoAb-fS) and the values of protein S activity (S-act) were not statistically different between patients and controls. C4b-binding protein values were not different from control values. In patients, PEG-fS values were lower than MoAb-fS values. Ten patients had a PEG-fS deficiency, 4 patients had a MoAb-fS deficiency and 8 had a S-act deficiency. Protein S activity and MoAb-fS were lower in clinical groups with poor prognosis and in patients with AIDS but PEG-fS was not. A trend for reduced S-act/MoAb-fS ratios was observed in patients. PEG-fS was negatively correlated with anticardiolipin antibody titers whereas MoAb-fS was not. The plasma of PEG-fS deficient HIV-patients contained high amounts of flow cytometry detectable microparticles which were depleted from plasma by PEG precipitation. The microparticles were partly CD42b and CD4 positive but CD8 negative. These microparticles were labelled by an anti free protein S monoclonal antibody. The observed differences between MoAb-fS and PEG-fS values were correlated with the amount of detectable plasma microparticles, just like the differences between MoAb-fS and S-act. Plasma microparticles correlated with anticardiolipin antibody titers.In summary, free protein S antigen in HIV infected patients is underestimated when the PEG precipitation technique is used due to the presence of elevated levels of microparticles that bind protein S. The activity of free protein S is also impaired by high levels of microparticles. The prevalence of free protein S deficiency in HIV positive patients is lower than previously published (4/38, -10%) and is correlated with poor prognosis. By implication, use of a PEG precipitation technique might give artefactually low free protein S antigen values in other patient groups if high numbers of microparticles are present. In HIV patients, high titers of anticardiolipin antibodies are associated with high concentrations of cell-derived plasma microparticles.

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Anticardiolipin Antibodies in Acute Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648530 ◽

1992 ◽

Vol 67 (06) ◽

pp. 724-724 ◽

Cited By ~ 15

Author(s):

O Bongard ◽

G Reber ◽

H Bounameaux ◽

P de Moerloose

Keyword(s):

Venous Thromboembolism ◽

Anticardiolipin Antibodies ◽

Acute Venous Thromboembolism

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Thrombin Generation Measured Ex Vivo Following Microvasculor Injury Is Increased in SLE Patients with Antiphospholipid-protein Antibodies

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657710 ◽

1997 ◽

Vol 78 (04) ◽

pp. 1173-1177 ◽

Cited By ~ 15

Author(s):

Jacek Musiał ◽

Jakub Swadźba ◽

Miłosz Jankowski ◽

Marek Grzywacz ◽

Stanisława Bazan-Socha ◽

...

Keyword(s):

Lupus Erythematosus ◽

Thrombin Generation ◽

Ex Vivo ◽

Skin Incision ◽

Anticardiolipin Antibodies ◽

Small Blood Vessel ◽

Anionic Phospholipids ◽

Increased Risk ◽

High Concentrations

SummaryAntiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and (β2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. However, the pathogenic mechanism leading to thrombosis in patients with APA remains unclear. We studied 32 patients with systemic lupus erythematosus (SLE) who were divided into two groups depending on the presence (n = 19) or absence (n = 13) of APA. Healthy volunteers (n = 12) matched by age and sex served as controls. In all subjects LA and IgG class anticardiolipin antibodies (ACA) were determined. Thrombin generation was monitored ex vivo measuring fibrinopeptide A (FPA) and prothrombin fragment F1 + 2 (F1 + 2) in blood emerging from a skin microvasculature injury, collected at 30 second intervals. In subjects with antiphospholipid antibodies mean FPA and F1 + 2 concentrations were signiF1cantly higher at most blood sampling times than in controls. In some SLE patients with APA the process of thrombin generation was clearly disturbed and very high concentrations of F1brinopeptide A were detected already in the F1rst samples collected. Two minutes after skin incision SLE patients without APA produced slightly more FPA, but not F1 + 2, as compared to healthy subjects. Mathematical model applied to analyze the thrombin generation kinetics revealed that APA patients generated signiF1cantly greater amounts of thrombin than healthy controls (p = 0.02 for either marker). In contrast, in the same patients generation of thrombin in recalciF1ed plasma in vitro was delayed pointing to the role of endothelium in the phenomenon studied. In summary, these data show for the F1rst time that in SLE patients with antiphospholipid-protein antibodies thrombin generation after small blood vessel injury is markedly increased. Enhanced thrombin generation might explain thrombotic tendency observed in these patients.

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Lupus anticoagulant, anticardiolipin antibodies, and human immunodeficiency virus in haemophilia.

Journal of Clinical Pathology ◽

10.1136/jcp.42.6.629 ◽

1989 ◽

Vol 42 (6) ◽

pp. 629-633 ◽

Cited By ~ 24

Author(s):

H Cohen ◽

I J Mackie ◽

N Anagnostopoulos ◽

G F Savage ◽

S J Machin

Keyword(s):

Human Immunodeficiency Virus ◽

Lupus Anticoagulant ◽

Anticardiolipin Antibodies ◽

Immunodeficiency Virus

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FRI0154 SHOULD BE OLDER PATIENTS TESTED FOR ANTIPHOSPHOLIPID ANTIBODIES? 695 CASES FROM THE RETROSPECTIVE SERIES HIBISCUS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6417 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 661.2-661

Author(s):

C. Belizna ◽

O. Latino ◽

L. Stojanovich ◽

P. Saulnier ◽

K. Devreese ◽

...

Keyword(s):

Relapse Rate ◽

Antiphospholipid Antibodies ◽

Older Patients ◽

Clinical Laboratory ◽

Late Onset ◽

Recurrent Stroke ◽

Therapeutic Option ◽

International Study ◽

Anticardiolipin Antibodies ◽

Male Predominance

Background:Although guidelines do not recommend antiphospholipid antibodies testing after 60 yo, recent data reported late onset antiphospholipid syndrome (APS).Objectives:To comparatively analyse the clinical, laboratory features and outcomes in 695 cases with primary APS between patients older and younger than 70 yo.Methods:we have performed an international study within the framework of the International Registry of primary APS patients treated with Hydroxychloroquine, HIBISCUS (an ongoing retrospective and prospective register launched in 2016). 28 centres from 17 countries participate. Data about late onset APS were analysed in 695 patients and were obtained from a standardized form registered in the database containing 66 items with respect to demographics, clinical and biological features.Results:Arterial events and especially stroke represented the main initial and recurrent clinical manifestation in 40 primary APS patients older than 70 yo. There were not statistically significant differences with respect to cardiovascular risk factors between the two groups of patients. A significant male predominance, a familial APS history, a higher prevalence of triple positivity, lower complement levels, and anticardiolipin antibodies (aCL) IgA isotype were found in older patients. Low anticoagulation regimens were safe and efficient, with a low relapse rate in older patients.Conclusion:we suggest that the detection of aPL antibodies should be included into the initial screening panel tests in elderly with thrombotic events, especially arterial, in particular those with recurrent stroke and familial APS.Our study further suggests that lower intensity anticoagulation regimens could be a therapeutic option in older APS patients, as no differences in outcomes and relapse rate were found between patients with high and low intensity anticoagulation regimens.References:[1]Grimaud F et al. Rheumatology. 2019;58:1006-10.[2]Goldman-Mazur S et al. Thromb Res. 2019;176:67-73.[3]Hirmerova J et al. 2017;36:167-73.Disclosure of Interests:Cristina Belizna: None declared, Omar Latino: None declared, Ljudmila Stojanovich: None declared, Patrick Saulnier: None declared, Katrien Devreese: None declared, Sebastien Udry: None declared, Natasa Stanisavljevic: None declared, Aleksandra Djokovic Speakers bureau: KRKA, Astra Zeneca, Actavis, Jaume Alijotas-Reig: None declared, Enrique Esteve-Valverde: None declared, Raquel Ferrer-Oliveras: None declared, Angela Tincani: None declared, Laura Andreoli: None declared, Francesca Regola: None declared, Maarten Limper: None declared, Alexander Makatsariya: None declared, Jamilya Khizroeva: None declared, Viktoria Bitsadze: None declared, Cecilia Chighizola: None declared, Francesca Pregnolato: None declared, Maria Orietta Borghi: None declared, Pier Luigi Meroni: None declared

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