Expression of the receptor activator of nuclear factor-kB ligand in peripheral blood mononuclear cells in patients with acute Charcot neuroarthropathy.

Introduction. The receptor activator of nuclear factor-kB (RANK), ligand (RANK-L) and osteoprotegerin (OPG) are implicated in the pathogenesis of acute Charcot neuroarthropathy (CN). Materials and Methods. This study aimed to investigate the expression of RANK-L and OPG in peripheral blood mononuclear cells (PBMC) from patients with acute CN. Results. We found that the expression of RANK-L was lower in patients with acute CN as compared with diabetic control subjects and healthy control participants; whereas OPG expression was not detected in patients and in both control groups. RANK-L expression at the onset of disease was inversely correlated with the index of polyunsaturation (PUI), a bone marrow MRS-derived measurable index that allows evaluation of disease activity in acute CN, and recovery time. Finally, the expression of RANK-L increased at the time of healing compared with the values found during the acute phase. Conclusions. In conclusion, our preliminary data provide a first step in applying analysis of RANK-L expression in peripheral blood cells to the diagnosis of acute CN. Based on our data we also suggest that analysis of RANK-L expression could be a complementary tool that can be employed to obtain quantitative parameters that may help clinicians to monitor disease activity in patients with acute CN.

Increased CD4 and CCR5 expression and human immunodeficiency virus type 1 entry in CD40 ligand-stimulated macrophages.

The effects of a soluble trimeric CD40 ligand (CD40L) agonist on the expression of CD4 and CCR5 and on human immunodeficiency virus (HIV) type 1 entry into and replication in human macrophages were investigated. CD40L increased the number of CD4 and CCR5 antibody-binding sites and the percentage of CD4- and CCR5-expressing cells. Infection of CD40L-stimulated macrophages with HIV-1 resulted in a marked increase of viral DNA with respect to controls, as demonstrated by polymerase chain reaction assay. HIV-1 p24 antigen analysis showed that peak viral production did not differ between CD40L-stimulated macrophages and controls. However, because of a prolonged life span, overall viral output was increased in CD40L-stimulated cultures. In addition, CD40L down-regulated the antiviral efficacy of compounds that inhibit HIV-1 reverse transcriptase. In conclusion, CD40L stimulation of macrophages can contribute to plasma virus load and favor the establishment of a pool of latently infected macrophages that can be reactivated to release virus.