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The antiphospholipid syndrome (APS) is characterized by recurrent arterial and/or
venous thromboses, pregnancy loss and the presence of antiphospholipid antibodies
(aPL). One of the discussed mechanisms of this thrombotic activity in APS patients
is attributed to TNFalpha secretion in monocytes after aPL stimulation. To investigate
this mechanism in detail, we employed a monoclonal aPL and IgG fractions of APS patients
for stimulation of human peripheral monocytes. Stimulation with this monoclonal aPL
resulted in an increased expression and secretion of TNFalpha, caused by specific
upregulation of TLR8 mRNA and protein expression levels. To confirm the specificity
of this finding we could demonstrate that the TNFalpha enhancement could be neutralized
by a TLR8-specific inhibitory DNA-oligonucleotide and could be further increased by
adding the specific ligands for TLR8. Using APS patients IgG fractions for stimulation
of peripheral monocytes revealed a similar TLR8 mRNA elevation and increase in TNFalpha-production.
Furthermore the TLR8 expression level in PBMC's of APS patients was as well significantly
elevated. It could be demonstrated that the TNFalpha release in monocytes resulting
from aPL stimulation was exclusively induced by TLR8 engagement. This could be confirmed
in PBMC's of APS patients, hinting that endogenous stimulation of TLR8 in APS patients
and consecutive elevation of TNFalpha promotes a proinflammatory environment.
2009 Elsevier GmbH. All rights reserved.