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Identification of microRNAs Potentially Involved in Primary Antiphospholipid Syndrome Related Thrombosis

C. Oliveira Vaz1, M. Vieira Geraldo1, L. Ferreira Alves1, P.E. Nascimento Silva Vasconcelos1, M. Aparecida Cursino1, J. Coelho França Quintanilha1, L. Brito Bastos1, G.L. Tripiquia Vechiatto Mesquita1, B. Cardoso Jacintho1, A.P. Rosa dos Santos1, N. Godoy Torso1, J. Marques de Oliveira2, T. Sereno Cobaxo1, A. Aparecido Geraldo1, J. Bassani Borges3, R.C. Costa de Freitas3, J.M. Annichino-Bizzacchi1, B. Moraes Mazetto1, P. Moriel1, F. Loureiro de Andrade Orsi1

1University of Campinas (UNICAMP), Campinas, Brazil, 2University of Campinas, Campinas, Brazil, 3University of São Paulo, São Paulo, Brazil

Abstract Number: PB1914

Meeting: ISTH 2020 Congress

Theme: Thrombotic Microangiopathies » Antiphospholipid Syndrome

Background: The mechanisms behind the severe hypercoagulable state in Antiphospholipid Syndrome (APS) are not fully elucidated. Some individuals with persistent antiphospholipid antibodies (aPL) remain asymptomatic whereas others develop thrombotic complications, which suggests that the presence of aPL is not sufficient to trigger thrombosis.

Aims: The aim of this study was to evaluate the association between miRNAs, which are small non-coding simple chair RNA molecules, with thrombosis in patients with primary APS (t-PAPS).

Methods: In this exploratory study, t-PAPS patients and controls were enrolled at the Hematology Center at University of Campinas, Brazil. Plasma miRNAs were extracted using miRNeasySerum/Plasma Kit (Qiagen). Differentially expressed miRNAs were identified by MicroArray analysis in Affymetrix workstation. Functional analysis were performed using Transcriptome Analysis Console TM, Ingenuity Pathway AnalysisTM and Cytoscape softwares. Local Ethical Committee (CAAE: 83102317.5.0000.5404).

Results: 21 t-PAPS and 21 controls we included. The mean age was 40 (SD 12) in controls and 37 (SD 13) in patients, 52% of patients and controls were women and cardiovascular risk factors were more prevalent among t-PAPS (43% versus 10%). Clinical and laboratory features of t-PAPS are shown in Table 1. 24 miRNAs were differentially expressed between the two groups; 19 were up-regulated and five were down-regulated in t-PAPS as compared to controls. Only one (has-miR-4516) has been described in APS before. Together, the miRNAs have 1978 validated targets. Figure 1 shows the potential biological interactions between the miRNAs, their targets and pathways that can explain APS-related thrombosis. Particularly, five miRNAs regulate the expression of natural anticoagulants (tissue factor pathway inhibitor, antithrombin, thrombomodulin) and five regulate the expression of complement inhibitors.

Conclusions: We identified 24 miRNAs differentially expressed between t-PAPS and controls that are potentially involved in the regulation of coagulation and complement cascade. Presence of miRNAs and their and potential pathological mechanisms will be confirmed in a larger PAPS population.

Age in the diagnosis, mean (standard deviation) 33 (16)
Non-provoked thrombosis,n (%) 15 (71,4)
Venous thrombosis, n (%) 11 (52,4)
Multiple thrombosis, n (%) 6 (28,6)
Time elapsed since the last thrombosis in months, mean (standard deviation) 34.3 (28.4)
Lupus anticoagulante, n (%) 21 (100,0)
Anticardiolipin antibody IgM (%) 3 (14,3)
Anticardiolipin antibody IgG (%) 9 (42,8)
Anti-β2-glycoprotein I antibody (%) 16 (76,2)
Triple positivity for aPL, n (%) 9 (42,8)

[Table 1. Clinical and laboratory features of t-PAPS n=21]


[Figure 1. Predicts interactions between microRNAs target genes in biological context (confidence index > 0.8)]

To cite this abstract in AMA style:

Oliveira Vaz C, Vieira Geraldo M, Ferreira Alves L, Nascimento Silva Vasconcelos PE, Aparecida Cursino M, Coelho França Quintanilha J, Brito Bastos L, Tripiquia Vechiatto Mesquita GL, Cardoso Jacintho B, Rosa dos Santos AP, Godoy Torso N, Marques de Oliveira J, Sereno Cobaxo T, Aparecido Geraldo A, Bassani Borges J, Costa de Freitas RC, Annichino-Bizzacchi JM, Moraes Mazetto B, Moriel P, Loureiro de Andrade Orsi F. Identification of microRNAs Potentially Involved in Primary Antiphospholipid Syndrome Related Thrombosis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/identification-of-micrornas-potentially-involved-in-primary-antiphospholipid-syndrome-related-thrombosis/. Accessed October 1, 2023.

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