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MULTICENTRE STUDIES

SOLUBLE CD40 LIGAND IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES

 

COORDINATORS

 

Ferro D, Loffredo L, Violi F, G. Valesini.

IV Divisione  Clinica Medica, Policlinico Umberto I, Università “La Sapienza”, Rome, Italy

 

 

PROJECT

 

CD40 Ligand (CD40L) is a protein of Tumor Necrosis Factor family that exerts inflammatory and prothrombotic activity upon the interaction with its receptor CD40. It is calculated that more than 95% of soluble CD40L (sCD40L) is of platelet origin:

In the setting of atherosclerosis several studies demonstrated that elevated levels of sCD40L increase the risk for cardiovascular disease.

Previous studies demonstrated that patients with systemic lupus erythematosus (SLE) have elevated circulating levels of sCD40L and suggested that this finding could be relevant for the progression of the disease via stimulation of B cells by CD40L interaction with its receptor CD40. In a preliminary report we demonstrated that sCD40L is more elevated in SLE with antiphospholipid antibodies (aPL+) compared with those without antiphospholipid antibodies (aPL-); the specificity of this finding was corroborated by the lack of difference in disease activity, that could affect the levels of sCD40L in the two subgroups. Interestingly, SLE aPL+ patients with history of thrombosis had higher circulating sCD40L levels than SLE aPL+ with no history of thrombosis; conversely subjects with previous thrombosis free of SLE and aPL- showed normal sCD40L. As sCD40L is known to exert a prothrombotic effect, the enhanced circulating levels of sCd40L may represent a novel mechanism accounting for thrombosis in the setting of the antiphospholipid syndrome.

We propose a multicenter study which include:

-         aPL positive SLE patients with and without thrombosis

-         aPL negative SLE patients with and without thrombosis

-         non SLE aPL positive patients with and without thrombosis

-         non SLE aPL negative patients with thrombosis

-         aPL negative anti beta 2 positive patients

-         healthy subjects

The study should explore the following issues:

1)      Is sCD40L elevated in patients with primary or secondary antiphospholipid syndrome?

2)      Is sCD40L related to markers of clotting activation?

3)      Is sCD40L predictive of thrombosis?

 

For additional information and applications, please e-mail: francesco.violi@uniroma1.it

Web contens: EWPSLE Info Desk.

 

Last updated: 30 November 2005