Endothelial progenitor dysfunction associates with a type I interferon signature in primary antiphospholipid syndrome
| Autor: | W. Joseph McCune, Diego F. Hernández-Ramírez, Srilakshmi Yalavarthi, Nayef M. Kazzaz, Carlos A. Núñez-Álvarez, Paula L. Bockenstedt, Alex A. Gandhi, Robert C. Grenn, Jason S. Knight, Antonio R. Cabral |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Cellular differentiation Immunology Alpha interferon Receptor Interferon alpha-beta Peripheral blood mononuclear cell Article General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences 0302 clinical medicine Rheumatology Interferon Antiphospholipid syndrome medicine Humans Immunology and Allergy Progenitor cell Aged Endothelial Progenitor Cells Progenitor 030203 arthritis & rheumatology business.industry Interferon-alpha Cell Differentiation Middle Aged Antiphospholipid Syndrome Flow Cytometry medicine.disease Antibodies Neutralizing 030104 developmental biology Case-Control Studies Interferon Type I Leukocytes Mononuclear Female business Interferon type I medicine.drug |
| Zdroj: | Annals of the Rheumatic Diseases. 76:450-457 |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | ObjectivesPatients with antiphospholipid syndrome (APS) are at risk for subclinical endothelial injury, as well as accelerated atherosclerosis. In the related disease systemic lupus erythematosus, there is a well-established defect in circulating endothelial progenitors, which leads to an accrual of endothelial damage over time. This defect has been at least partially attributed to exaggerated expression of type I interferons (IFNs). We sought to determine whether these pathways are important in APS.MethodsWe studied 68 patients with primary APS. Endothelial progenitors were assessed by flow cytometry and functional assay. Type I IFN activity was determined by a well-accepted bioassay, while peripheral blood mononuclear cells were scored for expression of IFN-responsive genes.ResultsEndothelial progenitors from patients with APS demonstrated a marked defect in the ability to differentiate into endothelial cells, a phenotype which could be mimicked by treating control progenitors with APS sera. Elevated type I IFN activity was detected in the circulation of patients with APS (a finding that was then replicated in an independent cohort). While IgG depletion from APS sera did not rescue endothelial progenitor function, the dysfunction was successfully reversed by a type I IFN receptor-neutralising antibody.ConclusionsWe describe, for the first time to our knowledge, an IFN signature in primary APS and show that this promotes impaired endothelial progenitor function. This work opens the door to novel approaches that may mitigate vascular damage in APS, such as anti-IFN drugs. |
| Databáze: | OpenAIRE |
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