Estudio de los niveles de ligando CD40 en pacientes con síndrome coronario agudo

Introduction

The CD40 ligand (CD40L) is a member of the tumor necrosis factor superfamily and plays an important role in the regulation of thymus-dependent humoral immunity and cell-mediated immune responses. This ligand is a 39 kDa, 261 amino acid (aa) glycoprotein that can form either homotrimers or undergo proteolytic cleavage to produce soluble forms of CD40 (i.e. 15-18 KDa). Elevated levels of soluble CD40L (sCD40L) have been observed in the sera of patients with systemic lupus erythematosus, chronic lymphocytic leukemia and unstable angina. Enhanced levels of both soluble and membrane-bound CD40L in angina patients suggest that CD40L plays a pathogenic role in the atherosclerotic process and in promoting acute coronary syndromes (ACS).

Material and methods

We analyzed serum sCD40L levels in 56 patients with ACS (aged 54.4 ± 13.4 years) from the internal medicine department of our hospital compared with levels in 22 healthy controls (aged 43 ± 8 years). To measure sCD40 we used the Quantikine CD40 ligand immunoassay, a solid-phase ELISA designed to measure human CD40 in serum using E. coli-expressed recombinant human CD40. For comparison purposes, troponin T data was measured in patients with ACS. These data were obtained by a chemiluminescent method using the Elecsys 2100 Roche Diagnostics analyzer.

Results

Mean values of CD40L were significantly higher in healthy controls (546.7 ± 64.7 pg/mL) than in ACS patients: 1,048 ± 157 pg/mL (p < 0.05). The comparison study between troponin T and CD40L generated the following regression equation: Troponin T = 1.48 * CD40L - 0.004.

Discussion

The proinflammatory and procoagulant protein CD40L represents a novel target in the treatment of atherosclerosis and ACS. Currently, risk evaluation in patients with ACS can be carried out by troponin analysis. Although troponins are only markers of myocardial necrosis, sCD40L is a marker of platelet activation and unstable plaques and can thus be used to identify disease activity before the development of cardiac cell necrosis.