Article Text

Download PDFPDF
Extended report
Endothelial progenitor dysfunction associates with a type I interferon signature in primary antiphospholipid syndrome
  1. Robert C Grenn1,
  2. Srilakshmi Yalavarthi1,
  3. Alex A Gandhi1,
  4. Nayef M Kazzaz1,
  5. Carlos Núñez-Álvarez2,
  6. Diego Hernández-Ramírez2,
  7. Antonio R Cabral2,3,
  8. W Joseph McCune1,
  9. Paula L Bockenstedt4,
  10. Jason S Knight1
  1. 1Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  2. 2Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  3. 3Division of Rheumatology, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
  4. 4Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
  1. Correspondence to Dr Jason S Knight, Division of Rheumatology, University of Michigan, 5520A MSRB1, 1150 W Medical Center Drive, SPC 5680, Ann Arbor, MI 48109-5680, USA; jsknight{at}


Objectives Patients 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.

Methods We 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.

Results Endothelial 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.

Conclusions We 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.

  • Antiphospholipid Syndrome
  • Atherosclerosis
  • Cytokines

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Handling editor Tore K Kvien

  • RCG and SY contributed equally.

  • Twitter Follow Jason Knight at @jasonsknight

  • Contributors RCG, SY, AAG, NMK, CN-A and DH-R conducted experiments and analysed data. ARC, WJM, PLB and JSK analysed data and designed the study. All authors participated in writing the manuscript, and gave approval before submission.

  • Funding JSK was supported by NIH K08AR066569 and a career development award from the Burroughs Wellcome Fund. NMK received funding from the Security Forces Hospital Program, Ministry of Interior, Riyadh, Saudi Arabia. WJM and the Michigan Lupus Cohort were supported by the Mary Piazza Lupus Research Fund and the Michael and Marcia Klein Lupus Research Fund.

  • Competing interests None declared.

  • Ethics approval University Institutional Review Boards.

  • Provenance and peer review Not commissioned; externally peer reviewed.