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

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

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1139906

DOI=10.3389/fmed.2023.1139906

ISSN=2296-858X

ABSTRACT=<p>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 <italic>ANXA3, TNFAIP6, TXK, BACH2</italic>, and <italic>SERPINB2</italic> genes has been associated with both arterial and venous thrombosis in the general population. Therefore, the aim of this study was to examine whether <italic>ANXA3, TNFAIP6, TXK, BACH2</italic>, and <italic>SERPINB2</italic> 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 <italic>ANXA3</italic> (<italic>P</italic> = 0.008) and <italic>TNFAIP6</italic> (<italic>P</italic> = 0.001) and decreased expression of the <italic>TXK</italic> gene (<italic>P</italic> = 0.0001) were associated with an increased risk of t-PAPS compared to the control. <italic>ANXA3</italic> 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. <italic>ANXA3</italic>, <italic>TNFAIP6</italic>, <italic>TXK, BACH2</italic>, and <italic>SERPINB2</italic> expression levels were also similar between aPL carriers and controls (<italic>P</italic> = 0.77; <italic>P</italic> = 0.48; <italic>P</italic> = 0.08; <italic>P</italic> = 0.73, and <italic>P</italic> = 0.13, respectively). In conclusion, our results showed that genes related to hemostasis (<italic>ANXA3</italic>) and immunity (<italic>TNFAIP6</italic>, <italic>TXK</italic>) 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.</p>