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

Two proteins, apolipoprotein D and RNase2, studied within the confirmation arm of our work did not show differences between UTC and UTI. Apolipoprotein D has many functions, but has been most widely studied within the context of lipid metabolism and neurological disease. 40 However, it may also play a role in modulation of inflammation in the setting of infection. 41 Apolipoprotein D is a lipocalin 40 and as such may bind ligands with implications in the innate immune system. However, the known ligands for apolipoprotein D consist mainly of lipids within high-density lipoproteins or plasma membranes. 42 Accordingly, most of the known functions of apolipoprotein D involve the neurological system. 42 There is scant literature on the utility of this protein in the setting of infection. It is possible that apolipoprotein D is present in the urine of patients with neurogenic bladder due to its role within the neurological system and underlying etiology of neurogenic bladder. RNase2, also known as eosinophil-derived neurotoxin, is a protein found in granules within eosinophils. While initially described in the urine, RNase2 was later found to have the same structure as eosinophil-derived neurotoxin, 43 a protein that is upregulated by Th2-driven allergic inflammation or parasitic infection. 43 Furthermore, RNase2 has anti-viral activity, specifically against single-stranded RNA viruses, 44 and can induce the migration of dendritic cells, but not neutrophils, monocytes, or T-cells. 45 While urinary RNase2 has been described in allergic 46 and parasitic diseases, 47 it has not been described in the context of bacterial infections. The presence of this protein in the urine of our patients may be related to dendritic cell migration. While there is no statistical significance in this protein, there were several patients in the UTI group with elevated levels of RNase2 although no differences in the median concentration. Further work is needed to understand the role, if one exists, of RNase2 in UTIs.