Glomerular, Tubular, and Urinary Immune Complexes (ICs) in IgA Nephropathy (IgAN): High-Resolution Image Analysis and ELISA Studies
L Novak, H Suzuki, Z Vernerova, I Rychlik, J Novak, BA Julian. University of Alabama at Birmingham, Birmingham; Charles University, Prague, Czech Republic
Background: IgAN patients have glomerular IgA1-containing deposits originating from circulating ICs composed of aberrantly glycosylated IgA1 bound by anti-glycan antibodies (IgG or IgA1). We hypothesized that these circulating ICs may escape hepatic clearance, deposit in the glomeruli, and induce renal injury. Furthermore, a fraction of these ICs may be excreted in the urine. The properties of these renal immune deposits have not been well studied in terms of the pattern, co-localization of the components, and presence in tubuli.
Design: Frozen renal biopsy specimens from 10 randomly selected IgAN patients were stained with fluorochrome-labeled antibodies against IgG, IgA, and C3. For seven patients, urine was obtained contemporaneously, i.e., just before renal biopsy. Urinary IgA-IgG complexes were measured by ELISA. The distribution and pattern of ICs deposited in mesangium and tubuli were examined with a confocal microscope.
Results: Mesangial ICs had typical irregular surface and variable size. Electron microscopy confirmed the distribution of ICs in glomeruli. Comparing data from confocal microscopy with results of routine immunofluorescence staining in pathology reports, glomerular IgG deposits were detected in 60% vs. 40% specimens (> 1+ intensity), respectively. Confocal microscopy showed tubular IgG and IgA deposits that were co-localized in 80% specimens, whereas 20% had neither immunoglobulin in tubuli. Aggregates of small ICs present in tubular lumen and adjacent to tubular epithelium represented the predominant pattern of the tubular ICs. Two biopsies showed cast-like tubular structures. All tubular ICs displayed IgA-IgG colocalization. Complement C3 was also co-localized in these ICs except in two biopsies. ELISA data confirmed presence of IgA-IgG ICs in all seven contemporaneously collected urine samples. Levels of urinary IgA-IgG ICs correlated with proteinuria, but not with the intensity of IgG staining in tubuli or glomeruli.
Conclusions: In summary, this study confirmed the presence of IgA-IgG ICs in renal tubules and in the urine of patients with IgAN.
Category: Kidney (does not include tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 234, Wednesday Afternoon