Evaluation of a gene signature related to thrombotic manifestations in antiphospholipid syndrome

Bruna Cardoso Jacintho; Bruna de Moraes Mazetto Fonseca; Bidossessi Wilfried Hounkpe; Jose Diogo Oliveira; Ana Paula Rosa Dos Santos; Camila de Oliveira Vaz; Erich Vinicius de Paula; Fernanda Andrade Orsi

doi:10.3389/fmed.2023.1139906

Evaluation of a gene signature related to thrombotic manifestations in antiphospholipid syndrome

Front Med (Lausanne). 2023 Mar 23:10:1139906. doi: 10.3389/fmed.2023.1139906. eCollection 2023.

Authors

Bruna Cardoso Jacintho¹, Bruna de Moraes Mazetto Fonseca^{1

2}, Bidossessi Wilfried Hounkpe¹, Jose Diogo Oliveira¹, Ana Paula Rosa Dos Santos¹, Camila de Oliveira Vaz¹, Erich Vinicius de Paula^{1

2}, Fernanda Andrade Orsi^{2

3}

Affiliations

¹ School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.
² Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil.
³ Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.

Abstract

Thrombotic primary antiphospholipid syndrome (t-PAPS) is an acquired condition characterized by heterogeneous thrombotic manifestations, which is intriguing since venous and arterial thrombosis appear to have distinct pathogenesis. Gene expression analysis may constitute a new approach to evaluate potential similarities or differences between the clinical manifestations of t-PAPS. Recently, dysregulation of the ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 genes has been associated with both arterial and venous thrombosis in the general population. Therefore, the aim of this study was to examine whether ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression was associated with t-PAPS. Gene expression was quantified by qPCR of total leukocyte mRNA. In this case-control study, 102 t-PAPS patients, 17 asymptomatic antiphospholipid (aPL) carriers and 100 controls were evaluated. Increased expression of ANXA3 (P = 0.008) and TNFAIP6 (P = 0.001) and decreased expression of the TXK gene (P = 0.0001) were associated with an increased risk of t-PAPS compared to the control. ANXA3 upregulation was more evident in cases of arterial thrombosis and multiple thrombotic events. There was no difference in the expression of these genes between triple and non-triple aPL positivity. ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression levels were also similar between aPL carriers and controls (P = 0.77; P = 0.48; P = 0.08; P = 0.73, and P = 0.13, respectively). In conclusion, our results showed that genes related to hemostasis (ANXA3) and immunity (TNFAIP6, TXK) are dysregulated in t-PAPS compared to controls. Gene dysregulation was not detected in aPL carriers and was not related to the aPL profile, suggesting that this gene signature is related to thrombotic manifestations rather than to aPL burden. Our results suggest that innate immunity and hemostasis pathways are associated with t-PAPS at a molecular level and may play a role in disease severity.

Keywords: antiphospholipid antibody; antiphospholipid syndrome; gene expression; mRNA; thrombosis.

Grants and funding

This study was funded by the São Paulo Research Foundation–FAPESP (grant number: 2016/14172-6) and the National Council for Scientific and Technological Development-CNPq (grant number: 43833902018-5). BJ received financial support from FAPESP (grant numbers: 2019/20136-0 and 2021/07150-4) and the Coordination for the Improvement of Higher Education Personnel (CAPES)–88887.499972/2020-00.