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Innate immune response gene expression profiles characterize primary antiphospholipid syndrome

Abstract

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder characterized by thromboembolic episodes and pregnant morbidity with an increasing clinical importance. To gain insight into the pathogenesis of PAPS, we have investigated the gene expression profiles that characterize peripheral blood mononuclear cells derived from PAPS patients. We show that the transcriptional activity of genes involved in innate immune responses, such as toll-like receptor 8 and CD14, as well as downstream genes of this pathway, such as STAT1, OAS2, TNFSF13 and PLSCR1 are significantly increased in PAPS patients. In addition, the expression of monocyte-specific cytokines is also elevated in PAPS mononuclear cells stimulated in vitro with lipopolysaccharide. Taken together, these results reveal a ‘response to pathogen’ signature in PAPS, which could reflect an altered monocyte activity. Finally, microarray analyses also revealed a reduced expression of genes coding for proteins involved in transcriptional control. Interestingly, a significant proportion of them exhibit E2F-binding sites in their promoter, suggesting that a deregulated RB/E2F activity could play a role in the pathogenesis of antiphospholipid syndrome.

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Acknowledgements

We are grateful to all the patients for their participation. We would like to thank Naiara Zorrilla, Nerea Liaño and Ainhoa Bolívar for their technical support, and Natalia Rivera for help with blood collection and patient characterization. This work has been supported by Spanish Ministry of Health grants (PI02/1561 to AMZ; PI02/0417 and PI05/0047 to M.L-H and PI05/0475 to VM-T), Basque Government grants (ETORTEK IE019 and SAIOTEK to AMZ); and Fundación Mutua Madrileña grant (ACI 01/05 to VM-T).

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Correspondence to A M Zubiaga.

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Bernales, I., Fullaondo, A., Marín-Vidalled, M. et al. Innate immune response gene expression profiles characterize primary antiphospholipid syndrome. Genes Immun 9, 38–46 (2008). https://doi.org/10.1038/sj.gene.6364443

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