TNF-alpha is a critical effector and a target for therapy in antiphospholipid antibody-induced pregnancy loss. Academic Article uri icon

Overview

abstract

  • The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, intrauterine growth restriction, and vascular thrombosis in the presence of antiphospholipid (aPL) Abs. Our studies in a murine model of APS induced by passive transfer of human aPL Abs have shown that activation of complement and recruitment of neutrophils into decidua are required for fetal loss, and emphasize the importance of inflammation in aPL Ab-induced pregnancy loss. In this study, we examine the role of TNF-alpha in pregnancy complications associated with aPL Abs in a murine model of APS. We show that aPL Abs are specifically targeted to decidual tissue and cause a rapid increase in decidual and systemic TNF-alpha levels. We identify the release of TNF-alpha as a critical intermediate that acts downstream of C5 activation, based on the fetal protective effects of TNF-alpha deficiency and TNF blockade and on the absence of increased TNF-alpha levels in C5-deficient mice treated with aPL Abs. Our results suggest that TNF-alpha links pathogenic aPL Abs to fetal damage and identify TNF blockade as a potential therapy for the pregnancy complications of APS.

publication date

  • January 1, 2005

Research

keywords

  • Antibodies, Antiphospholipid
  • Antiphospholipid Syndrome
  • Decidua
  • Tumor Necrosis Factor-alpha

Identity

Scopus Document Identifier

  • 10844288801

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.174.1.485

PubMed ID

  • 15611274

Additional Document Info

volume

  • 174

issue

  • 1