Reflux Nephropathy : Role of Bacterial Antigens and Urinary Proteins

Monoclonal antibodies (MoAbs) were raised against pyelonephritis-associated P-pili (PAP-pili) and Tamm-Horsfall glycoprotein (THGP). These MoAbs were μ-, κ-chain specific and reacted with polypeptides of 18 kD (PAP-pili) or 90 kD (THGP). The epitope of the MoAb directed against PAP-pili was present at the apical portion of the pilus. MoAbs against THGP recognized 4 distinct epitopes, and one MoAb stained immunofluorescent material inside both Bowmann's capsule and renal tubular cells on frozen sections from a kidney without obstructive or interstitial changes. Analysis of E. coli phenotypes with MoAbs against PAP-pili and with polyvalent 0 and KI antisera showed that organisms positive for PAP-pili, 01, and KI antigens were the more common causes of acute pyelonephritis. The chemiluminescence response of polymorphonuclear leukocytes was prominent following stimulation with 0 or K antigens isolated form pyelonephritic or enteropathogenic E. coli strains. Pyelonephritopathogenic E. coli may thus be a small number of strains which stimulate an energetic leukocyte response that produces more severe renal lesions. Pyelonephritis patients had high urinary free light chain levels regardless of the presence of vesicoureteral reflux or recurrent infection. THGP bound nonspecifically to these light chains and to IgA. In patients with reflux nephropathy, heavy tubular excretion of such proteins and their binding to THGP may interfere with urine outflow. Recurrent infection by virulent organisms and interactions between THGP and other urinary proteins may thus aggravate reflux nephropathy