Objective: Inflammation might represent a second hit for anti-phospholipid antibody (aPL)-mediated thrombosis. Inflammatory responses have been linked to gene polymorphisms of several cytokines and Toll Like Receptors (TLRs). We examined IL1β, TNFα, TGFβ, IL6, IFNγ, IL10, tlr4 gene polymorphisms in a family with several members positive for IgG anti-β2 glycoprotein I (β2GPI) antibodies but with recurrent thrombosis in one member only. Methods: Lupus anticoagulant, anti-cardiolipin, anti-β2GPI IgG/IgM antibodies, IL1β, TNFα, TGFβ1, IL6, IL10, IFNγ, tlr4 gene polymorphisms (by allele-specific polymerase chain reaction) in addition to standard thrombophilic risk factors and cytokine serum levels (IL-1β, TNFα, IL-10) were evaluated. Results: Recurrent thrombotic events was reported only in the proband, but not in three healthy siblings persistently positive for IgG anti-β2GPI antibodies, respectively. The wild type tlr4 gene and cytokine polymorphisms associated with a high pro-inflammatory response (IL-1β promoter-511 C/T; TNFα G/A; TGFβ + 10 T/C, +25 C/G; IL-6 -174 C/G) were found only in the proband. Serum cytokine levels were normal. Conclusion: This case report confirms that protective tlr4 gene polymorphisms are more frequent in asymptomatic aPL carriers. In line with the role of inflammatory mediators as second hits for aPL-associated thrombosis, the polymorphisms of cytokines linked to higher inflammatory response were found in the proband only.
|Titolo:||Pro-inflammatory genotype as a risk factor for aPL-associated thrombosis : report of a family with multiple anti-phospholipid positive members|
SCURATI, SILVIA (Secondo)
MERONI, PIERLUIGI (Penultimo)
|Parole Chiave:||Anti-beta2 glycoprotein I antibodies; Antiphospholipid syndrome; Cytokines; Toll Like Receptor|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||feb-2009|
|Appare nelle tipologie:||01 - Articolo su periodico|