Identification of Urinary CD44 and Prosaposin as Specific Biomarkers of Urinary Tract Infections in Children With Neurogenic Bladders

Forster, Catherine S; Haffey, Wendy D; Bennett, Michael; Greis, Kenneth D; Devarajan, Prasad

CD44, a type I transmembrane glycoprotein whose main ligand is hyaluronic acid, 23 is constitutively expressed in almost all tissues. 24 While initially believed to play a role in lymphocyte homing, 25 it has since been found to have multiple functions, including lymphocyte activation, cell-to-cell adhesion, hyaluron metabolism, embryonic development, cellular adhesion and migration, lymphocyte and monocyte proliferation and activation. [26] [27] [28] [29] [30] In this capacity, CD44 serves a role in the innate immune system, through both defense against pathogens 31 and stimulation of antimicrobial peptide production. 32 In addition, CD44 may also play a role in the pathogenesis of certain infections, including UTI. Indeed, Escherichia coli binds to CD44 in a hyaluronic acid-mediated mechanism and through this interaction invades urothelial cells. 33 Furthermore, CD44 knockout mice demonstrate increased bacterial clearance following transurethral inoculation compared with wild type, with no difference noted in neutrophil accumulation or activity. 33 However, the increase seen in urinary CD44 in this work is likely related to the fact that CD44 is constitutively expressed on the urothelial cells. 33 As one of the responses of the bladder to infection is exfoliation of superficial urothelial cells, 34 it is likely that the increased concentration of urinary CD44 seen in patients with UTI in this work is a result of the exfoliated urothelial cells.