Decreased Expression of Nicotinamide Phosphoribosyltransferase in Patients with Juvenile Idiopathic Arthritis Receiving Methotrexate

Abstract

To the Editor: Nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B cell colony-enhancing factor or visfatin, is an adipocytokine that has been identified as a proinflammatory mediator in cardiovascular disease, pulmonary inflammation, and sepsis1. Several roles have been ascribed to NAMPT including possible insulin mimetic properties, a part in the nicotinamide adenine dinucleotide (NAD) salvage pathway, and cytokine induction2,3,4,5. Recently, its effects have been studied in rheumatoid arthritis (RA), systemic lupus erythematosus, and systemic sclerosis6,7. NAMPT has been shown to be produced by synovial tissue, subintima, lymphocytes, and vascular endothelial cells7. In RA, it has been shown to activate human leukocytes, induce proinflammatory cytokines including interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), and protect fibroblasts and neutrophils from apoptosis, perpetuating inflammation and resulting in joint destruction7,8,9. NAMPT concentrations have also been shown to correlate with C-reactive protein levels and clinical disease activity in patients with RA8. APO866 is a molecule in development that inhibits the enzymatic function of NAMPT, leading to significantly lower levels of intracellular NAD, IL-1β, IL-6, and TNF-α in mice with collagen-induced arthritis10. This has garnered attention in studies of adults with rheumatic diseases but little research has been conducted in the pediatric population, particularly children with juvenile idiopathic arthritis (JIA). To determine if NAMPT inhibitors have the potential to affect pediatric disease, we tested the hypotheses that NAMPT concentrations are (1) increased in subjects with active arthritis, (2) decreased in patients treated with methotrexate (MTX), and (3) decreased by anti-TNF-α therapy in a cross-sectional cohort of patients with JIA. In a single-center cross-sectional study, plasma samples … Address correspondence to Dr E. Fox, Children’s Mercy Hospital, Department of Pediatrics, Graduate Medical Education, 2401 Gillham Road, Kansas City, MO 64108, USA. E-mail: ejfox{at}cmh.edu