Elevated Levels of the Cytokine LIGHT in Pediatric Crohn's Disease

Abstract

LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes), encoded by the TNFSF14 gene, is a cytokine belonging to the TNF superfamily. On binding to its receptors, herpes virus entry mediator and lymphotoxin β receptor, it activates inflammatory responses. We conducted this study to determine whether plasma LIGHT levels are elevated in Crohn's disease (CD) in a pediatric population with the aim of nominating this cytokine as a therapeutic target. We used a single-molecule immunoassay to determine the circulating levels of free LIGHT in plasma from pediatric patients with CD in our biobank (n = 183), a panel of healthy pediatric (n = 9) or adult (n = 22) reference samples, and pediatric biobank controls (n = 19). We performed correlational analyses between LIGHT levels and the clinical characteristics of the CD cohort, including age, Montreal classification, family history, medical/surgical therapy, and routine blood test parameters. LIGHT levels were greatly elevated in CD, with an average of 305 versus 32.4 pg/ml for controls from the biobank (p < 0.0001). The outside reference samples showed levels of 57 pg/ml in pediatric controls and 55 pg/ml in adults (p < 0.0001). We found a statistically significant correlation between white blood cell count and free LIGHT (p < 0.046). We conclude that free, soluble LIGHT is increased 5- to 10-fold in pediatric CD across an array of disease subtypes and characteristics.