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.

Pro-inflammatory genotype as a risk factor for aPL-associated thrombosis : report of a family with multiple anti-phospholipid positive members / V. De Angelis, S. Scurati, E. Raschi, A. Liutkus, A. Belot, M.O. Borghi, P.L. Meroni, R. Cimaz. - In: JOURNAL OF AUTOIMMUNITY. - ISSN 0896-8411. - 32:1(2009 Feb), pp. 60-63.

Pro-inflammatory genotype as a risk factor for aPL-associated thrombosis : report of a family with multiple anti-phospholipid positive members

S. Scurati
Secondo
;
E. Raschi;M.O. Borghi;P.L. Meroni
Penultimo
;
R. Cimaz
2009

Abstract

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.
Anti-beta2 glycoprotein I antibodies; Antiphospholipid syndrome; Cytokines; Toll Like Receptor
Settore MED/16 - Reumatologia
feb-2009
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/52083
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