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Evaluation of a Gene Signature Related to Thrombotic Manifestations in Antifospholipid Syndrome

1School of Medical Sciences, Department of Clinical Medicine, University of Campinas, Campinas, Brazil, 2School of Medical Sciences, University of Campinas, Campinas, Brazil, 3School of Medical Sciences, Department of Medical Physiopathology, Universisity of Campinas- UNICAMP, Campinas, Brazil, 4School of Medical Sciences, Department of Medical Sciences, University of Campinas,, Campinas, Brazil, 5Hematology and Hemotherapy Center, University of Campinas - UNICAMP, Campinas, Brazil, 6School of Medical Sciences, Department of Clinical Pathology, University of Campinas, Campinas, Brazil

Abstract Number: PB1059

Meeting: ISTH 2021 Congress

Theme: Venous Thromboembolism » Antiphospholipid Syndrome

Background: Whether different manifestations of thrombotic antiphospholipid syndrome (APS) share pathological mechanisms has not been established. Transcriptome analysis may constitute a new approach to evaluate the mechanisms behind thrombotic manifestations in APS.

Aims: To determine in patients with primary thrombotic APS (t-PAPS) the expression of genes already related to venous and arterial thrombosis in the general population.

Methods: mRNA was obtained from total leucocyte and gene expression was measured by qPCR and the results were analyzed by QuantStudio™ Software.

Results:

Table 2: Fold-change in individual studies (FC)
Genes Controls t-PAPS with venous thrombosis t-PAPS with arterial thrombosis t-PAPS with simple thrombosis t-PAPS with multiple thrombosis t-PAPS non-triple positive t-PAPS triple positive Main biological process
Up-regulated genes
TNFAIP6 0.93 1.38 1.49 1.27 2.17 1.33 1.85 Innate immunity
Down-regulated genes
SERPINB2 1.11 0.4 0.99 0.69 1.06 0.84 0.85 Hemostasis
BACH2 1.62 1.01 1.19 0.95 1.15 0.98 1.27 Immune regulation
TXK 1.44 0.86 0.94 0.84 0.97 0.90 0.77 Innate immunity

Clinical and laboratory features of t-PAPS (n = 83). Legend: Abbreviations: t-PAPS thrombotic primary antiphospholipid syndrome; IQR interquartile range; aPL antiphospholipid antibodies

Table 1:
Age at the diagnosis, median (IQR) 33 (24; 48)
Time elapsed since the last thrombotic event in months, median (IQR) 33.9 (11.6; 66.9)
Non-provoked thrombosis, n (%) 48 (57.8)
Site of the first thrombotic event:
          Venous thrombosis, n (%) 61 (73.5)
          Arterial thrombosis, n (%) 22 (26.5)
Multiple thromboses, n (%) 35 (42.2)
aPL triple positivity, n (%) 14 (16.8)

Median fold changes in gene expression according to the subgroups of clinical relevance of t-PAPS. Legend: This table demonstrates that TNFAIP6 mRNA expression is higher in all t-PAPS subgroups in comparison with controls, being particularly elevated in patients who had multiple thrombosis (P= 0,01). ANXA3 mRNA expression was slightly higher in t-PAPS than in controls but the difference was not statistically significant. SERPINB2 mRNA expression is lower in all t-PAPS subgroups in comparison with controls, being slightly decreased in patients who had simple thrombosis (P= 0,0025). BACH2 mRNA expression was lower in all t-PAPS subgroups in comparison with controls, being slightly decreased in patients who had a single thrombosis (P=0,002) TXK mRNA expression was lower in all t-PAPS subgroups in comparison with control, being slightly decreased in triple positive patients (P= < 0,0001).
83 t-PAPS and 85 controls were included. The median age at the enrollment day was 40 years-old (IQR 31 – 51) in patients and 38 (IQR 29 – 53) in controls, 66% of patients and controls were women and cardiovascular risk factors were more prevalent among t-PAPS than in controls (37% vs 11%). The clinical and laboratory features of t-PAPS patients are shown in Table 1. TXK (P<0.001), BACH2 (P=0.005) and SERPINB2 (P=0.003) mRNA expressions were down-regulated while TNFAIP6 mRNA expression was up-regulated (P=0.003) in t-PAPS when compared to controls. ANXA3 mRNA expression was similar between groups. In a subgroup analysis that considered different manifestations of t-PAPS, such as venous vs. arterial thrombosis, single vs. multiple thrombosis and non-triple positive vs. triple positive, we observed that the increase in TNFAIP6 mRNA expression was more pronounced in t-PAPS with recurrent thrombosis. Table 2 demonstrates the fold changes by t-PAPS subgroups.

Conclusions: In this study, we validated in t-PAPS the expression of genes previously associated with arterial and venous thrombosis in general population. Particularly, the main difference between t-PAPS and controls appeared in the expression of genes related to immune regulation. These genes were also associated with disease severity, such as multiple thrombosis and triple positivity. Our findings point towards an association between immune regulation and thrombosis in APS.
Acknowledgments: São Paulo Research Foundation FAPESP (2016/14172-6)  

To cite this abstract in AMA style:

Jacintho B, Mazetto B, Hounkpe B, Santos AP, Vaz C, Vechiatto G, Oliveira J, de Paula E, Orsi F. Evaluation of a Gene Signature Related to Thrombotic Manifestations in Antifospholipid Syndrome [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/evaluation-of-a-gene-signature-related-to-thrombotic-manifestations-in-antifospholipid-syndrome/. Accessed December 11, 2023.

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