Dataset Information

Cluster analysis for the identification of clinical phenotypes among antiphospholipid antibody-positive patients from the APS ACTION Registry.

ABSTRACT:

Objective

This study aimed to use cluster analysis (CA) to identify different clinical phenotypes among antiphospholipid antibodies (aPL)-positive patients.

Methods

The Alliance for Clinical Trials and International Networking (APS ACTION) Registry includes persistently positive aPL of any isotype based on the Sydney antiphospholipid syndrome (APS) classification criteria. We performed CA on the baseline characteristics collected retrospectively at the time of the registry entry of the first 500 patients included in the registry. A total of 30 clinical data points were included in the primary CA to cover the broad spectrum of aPL-positive patients.

Results

A total of 497 patients from international centres were analysed, resulting in three main exclusive clusters: (a) female patients with no other autoimmune diseases but with venous thromboembolism (VTE) and triple-aPL positivity; (b) female patients with systemic lupus erythematosus, VTE, aPL nephropathy, thrombocytopaenia, haemolytic anaemia and a positive lupus anticoagulant test; and (c) older men with arterial thrombosis, heart valve disease, livedo, skin ulcers, neurological manifestations and cardiovascular disease (CVD) risk factors.

Conclusions

Based on our hierarchical cluster analysis, we identified different clinical phenotypes of aPL-positive patients discriminated by aPL profile, lupus or CVD risk factors. Our results, while supporting the heterogeneity of aPL-positive patients, also provide a foundation to understand disease mechanisms, create new approaches for APS classification and ultimately develop new management approaches.

SUBMITTER: Zuily S

PROVIDER: S-EPMC8216235 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Cluster analysis for the identification of clinical phenotypes among antiphospholipid antibody-positive patients from the APS ACTION Registry.

Zuily Stéphane S Clerc-Urmès Isabelle I Bauman Cédric C Andrade Danieli D Sciascia Savino S Pengo Vittorio V Tektonidou Maria G MG Ugarte Amaia A Gerosa Maria M Michael Belmont H H Zamorano Maria Angeles Aguirre MAA Fortin Paul P Ji Lanlan L Efthymiou Maria M Cohen Hannah H Branch D Ware DW Jesus Guilherme Ramires de GR Nalli Cecilia C Petri Michelle M Rodriguez Esther E Cervera Ricard R Knight Jason S JS Atsumi Tatsuya T Willis Rohan R Bertolaccini Maria Laura ML Vega Joann J Wahl Denis D Erkan Doruk D

Lupus 20200723 11

<h4>Objective</h4>This study aimed to use cluster analysis (CA) to identify different clinical phenotypes among antiphospholipid antibodies (aPL)-positive patients.<h4>Methods</h4>The Alliance for Clinical Trials and International Networking (APS ACTION) Registry includes persistently positive aPL of any isotype based on the Sydney antiphospholipid syndrome (APS) classification criteria. We performed CA on the baseline characteristics collected retrospectively at the time of the registry entry o ...[more]

PMID: 32703117

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Project description:ObjectiveTo describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes.MethodsThe APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-β2 -glycoprotein I [anti-β2 GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity).ResultsThe 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-β2 GPI only.ConclusionOur study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.

Project description: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.

Dataset Information

Cluster analysis for the identification of clinical phenotypes among antiphospholipid antibody-positive patients from the APS ACTION Registry.

Objective

Methods

Results

Conclusions

Publications

Cluster analysis for the identification of clinical phenotypes among antiphospholipid antibody-positive patients from the APS ACTION Registry.

Similar Datasets

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