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Journal ArticleDOI: 10.1093/RHEUMATOLOGY/KEZ596

Identifying phenotypes of patients with antiphospholipid antibodies: results from a cluster analysis in a large cohort of patients

02 Mar 2021-Rheumatology (Rheumatology (Oxford))-Vol. 60, Iss: 3, pp 1106-1113
Abstract: OBJECTIVES To identify the aggregation of patients with aPL into different subgroups sharing common features in terms of clinical and laboratory phenotypes. METHODS We applied a hierarchical cluster analysis from the multiple correspondence analysis to determine subgroups of patients according to clinical and laboratory characteristics in a cohort of subjects with confirmed aPL positivity who presented to our outpatient clinics from 2006 to 2018. RESULTS A total of 486 patients [403 women; age 41.7 years (26)] were included, resulting in five clusters. Cluster 1 (n= 150) presented with thrombotic events (65.3% with venous thrombosis), with triple aPL positivity found in 34.7% of them (the highest rate among the different clusters). All the patients from cluster 2 (n = 91) had a confirmed diagnosis of SLE and the highest rate of anti-dsDNA positivity (91.7%). Cluster 3 included 79 women with pregnancy morbidity. Triple positivity was present in 3.8%, significantly lower when compared with Cluster 1 (34.7% versus 3.8%, P <0.01). Cluster 4 included 67 patients, 28 (41.8%) of whom with APS. Thrombotic events were observed in 23.9% patients. Cluster 4 had the highest rate of cytopenia, with thrombocytopenia as high 41.8% with no anti-dsDNA antibodies. Cluster 5 included 94 asymptomatic aPL carriers. CONCLUSION While clusters 1, 2, 3 and 5 corresponded to well-known entities, cluster 4 might represent a bridging condition between pure primary APS and defined SLE, with lower thrombotic risk when compared with primary APS but higher general features such as ANA and cytopenia (mainly thrombocytopenia).

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Topics: Outpatient clinic (52%), Cytopenia (51%)
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7 results found


Open accessJournal Article
Abstract: Antiphospholipid syndrome (APS) is a disorder characterised by recurrent arterial or venous thrombosis and/or pregnancy losses, in the presence of persistently elevated levels of anticardiolipin antibodies and/or evidence of circulating lupus anticoagulant (these abnormalities are detected by blood tests). Primary APS occurs when there is no evidence of associated diseases. APS in the presence of an underlying disease, usually systemic lupus erythematosus, is called secondary APS.

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40 Citations


Journal ArticleDOI: 10.1093/RHEUMATOLOGY/KEAA542
Yusuke Ogata1, Yuichiro Fujieda1, Masanari Sugawara1, Taiki Sato1  +6 moreInstitutions (1)
02 Mar 2021-Rheumatology
Abstract: Objective Using cluster analysis, to identify the subgroup of patients with APS with the poorest prognosis and clarify the characteristics of that subgroup. Methods This is a longitudinal retrospective cohort study of APS patients. Using clinical data and the profile of aPL, cluster analysis was performed to classify the patients into subgroups. Events were defined as thrombosis, severe bleeding, and mortality. Results A total of 168 patients with APS were included. Cluster analysis classified the patients into three subgroups; Cluster A (n = 61): secondary APS, Cluster B (n = 56): accumulation of cardiovascular risks and arterial thrombosis, Cluster C (n = 61): triple positivity of aPL and venous thrombosis. Cluster B showed significantly higher frequency of the events and higher mortality compared with the other clusters (P = 0.0112 for B vs A and P = 0.0471 for B vs C). Conclusion Using cluster analysis, we clarified the characteristics of the APS patients with the poorest prognosis. Risk factors for cardiovascular disease may further increase events in patients with APS.

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2 Citations


Journal ArticleDOI: 10.1016/J.AUTREV.2021.102798
Abstract: It is now widely accepted that antiphospholipid antibodies (aPL) have direct pathogenic effects and that B cells, notably through aPL production, play a key role in the development of antiphospholipid syndrome (APS). Recent findings strengthened the implication of B cells with the description of specific B cell phenotype abnormalities and inborn errors of immunity involving B cell signaling in APS patients. In addition, it has been shown in preclinical models that cross-reactivity between APS autoantigens and mimotopes expressed by human gut commensals can lead to B cell tolerance breakdown and are sufficient for APS development. However, B cell targeting therapies are surprisingly not as effective as expected in APS compared to other autoimmune diseases. Elucidation of the B cell tolerance breakdown mechanisms in APS patients may help to develop and guide the use of novel therapeutic agents that target B cells or specific immune pathway.

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Topics: B cell (54%), Antiphospholipid syndrome (51%)


Journal ArticleDOI: 10.1111/JTH.15518
Abstract: Background Although the triple positivity of antiphospholipid antibodies (aPL) is important for classifying high-risk patients, interpretation of aPL positivity, namely the lupus anticoagulant (LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein I autoantibodies (aB2GPI) remains challenging for thrombotic risk stratification. Objective To compare biological and clinical data between triple aPL- and single aCL-positive patients. Methods Of the 6500 patients assayed for aPL in daily practice within 3 years, we retrospectively analyzed data from 161 patients that were either triple aPL-positive or single aCL-positive with 5 years' follow-up for 121 of them. Results Whatever triple or single aPL positivity, we found a high prevalence of "carrier" patients (43%), which led us to question the clinical relevance of the triple aPL positivity. This result also justified the need to identify high-risk profiles. In asymptomatic patients, high risk of thrombotic events is associated with (1) two positive tests for LA or a Rosner Index >27 combined with both aCL-IgG and aB2GPI-IgG positivity, (2) persistent single aCL positivity without an associated autoimmune disease. In symptomatic patients, we demonstrated differences in the phenotype of patients and their therapeutic anticoagulation according to the number of positive aPL but we did not find differences in the number of clinical events, recurrence, or relapse, even in the absence of treatment. Conclusion This study shows that the thrombotic risk does not necessarily increase with the number of positive tests and raises the question of the therapeutic management of single aCL-positive patients.

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Open accessJournal ArticleDOI: 10.1002/ART.1780400928
Mph Marc C. Hochberg Md1Institutions (1)
Abstract: In 1982, the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology (ACR)published revised criteria for the classification of systemiclupus erythematosus (SLE) (1). During the ensuing decade several investigators, including Drs. Graham Hughes and Donato Alarcon-Segovia, among others, have described the presence and clinical associations or antiphospholipid antibodies in patients with SLE, as well as the occurrence of theprimary antiphospholipid syndrome (2-5). In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries (6).

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Topics: Lupus erythematosus (61%), Lupus vasculitis (54%)

9,016 Citations


Open accessJournal ArticleDOI: 10.1111/J.1538-7836.2006.01753.X
Spiros Miyakis1, Michael D. Lockshin2, Tatsuya Atsumi3, D W Branch4  +11 moreInstitutions (11)
Abstract: New clinical, laboratory and experimental insights, since the 1999 publication of the Sapporo preliminary classification criteria for antiphospholipid syndrome (APS), had been addressed at a workshop in Sydney, Australia, before the Eleventh International Congress on antiphospholipid antibodies In this document, we appraise the existing evidence on clinical and laboratory features of APS addressed during the forum Based on this, we propose amendments to the Sapporo criteria We also provide definitions on features of APS that were not included in the updated criteria

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Topics: Beta 2-Glycoprotein I (54%)

5,039 Citations


Journal ArticleDOI: 10.1093/COMJNL/41.8.578
Chris Fraley1, Adrian E. Raftery1Institutions (1)
Abstract: We consider the problem of determining the structure of clustered data, without prior knowledge of the number of clusters or any other information about their composition. Data are represented by a mixture model in which each component corresponds to a different cluster. Models with varying geometric properties are obtained through Gaussian components with different parametrizations and cross-cluster constraints. Noise and outliers can be modelled by adding a Poisson process component. Partitions are determined by the expectation-maximization (EM) algorithm for maximum likelihood, with initial values from agglomerative hierarchical clustering. Models are compared using an approximation to the Bayes factor based on the Bayesian information criterion (BIC); unlike significance tests, this allows comparison of more than two models at the same time, and removes the restriction that the models compared be nested. The problems of determining the number of clusters and the clustering method are solved simultaneously by choosing the best model. Moreover, the EM result provides a measure of uncertainty about the associated classification of each data point. Examples are given, showing that this approach can give performance that is much better than standard procedures, which often fail to identify groups that are either overlapping or of varying sizes and shapes.

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2,422 Citations


Open accessJournal ArticleDOI: 10.1002/ART.10187
Ricard Cervera, J.C. Piette, Josep Font, Munther A. Khamashta1  +24 moreInstitutions (10)
Abstract: Objective. To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression. Methods. The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database. Results. The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean +/- SD age of 42 +/- 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a higher frequency of stroke and angina pectoris, but a lower frequency of livedo reticularis, than the remaining patients. Conclusion. APS may affect any organ of the body and display a broad spectrum of manifestations. An association with SLE, the patient's sex, and the patient's age at disease onset can modify the disease expression and define specific subsets of APS.

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1,648 Citations


Open accessJournal Article

992 Citations


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