Increased Levels of Circulating IL-16 and Apoptosis Markers Are Related to the Activity of Whipple's Disease

Abstract

BackgroundWhipple's disease (WD) is an infectious disease caused by Tropheryma whipplei, which replicates in macrophages and induces the release of interleukin (IL)-16, a substrate of caspase 3, and macrophage apoptosis. The disease is characterized by intestinal, cardiac or neurological manifestations; its diagnosis is based on invasive analysis requiring tissue biopsies or cerebrospinal fluid puncture. The disease progression is slow and often complicated by relapses despite empirical antibiotic treatment.Methodology/Principal findingsWe monitored circulating levels of IL-16 and nucleosomes in 36 French patients with WD; among them, some patients were enrolled in a longitudinal follow-up. As compared to control subjects, the circulating levels of both IL-16 and nucleosomes were increased in untreated patients with WD presenting as intestinal, cardiac or neurological manifestations. This finding was specific to WD since the circulating levels of IL-16 and nucleosomes were not increased in patients with unrelated inflammatory diseases such as inflammatory bowel disease or Q fever endocarditis. We also found that increased levels of IL-16 and nucleosomes were related to the activity of the disease. Indeed, successful antibiotic treatment decreased those levels down to those of control subjects. In contrast, patients who suffered from relapses exhibited circulating levels of IL-16 and nucleosomes as high as those of untreated patients.Conclusions/SignificanceCirculating levels of both IL-16 and nucleosomes were increased in WD. This finding provides simple and non-invasive tools for the diagnosis and the prognosis of WD.