Abstract
INTRODUCTION: IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN) are considered similar diseases with different spectra of clinical manifestations. Routine immunofluorescence microscopy of kidney-biopsy specimens of patients with IgAN or IgAVN shows glomerular immune-complex deposits with IgA as (co)dominant immunoglobulin and variable staining for IgG. Complement C3 is usually present in both. To assess the relationships of the glomerular immune complexes in IgAN or IgAVN, we determined glomerular C3-IgA, C3-IgG, and IgA-IgG pairwise colocalization and correlated results with severity of kidney injury. METHODS: Sections of remnant frozen kidney biopsy specimens from patients with IgAN or IgAVN were stained with an IgG Fc-specific nanobody and antibodies specific for C3 or IgA. Staining was assessed by high-resolution confocal microscopy. Pairwise colocalization in immune-complex deposits was determined by imaging software and results were correlated with Oxford classification MEST-C scores. RESULTS: All samples had C3, IgA, and IgG in the glomerular immune-complex deposits, predominantly in mesangial areas, with additional peripheral capillary deposits in IgAVN greater than in IgAN. In IgAN, the mean values of the Pearson correlation coefficients were higher for C3-IgA than for C3-IgG or IgA-IgG; in IgAVN they were similar for C3-IgA and IgA-IgG. Furthermore, C3-IgA colocalization was similar in IgAN and IgAVN, whereas colocalizations of C3-IgG and IgA-IgG were higher in IgAVN than IgAN. In IgAN, but not IgAVN samples, greater C3-IgA colocalization was significantly associated with individual histologic features of active glomerular injury: mesangial hypercellularity, endocapillary hypercellularity, and cellular/fibrocellular crescents. Analyses using mixed-model repeated measures revealed a trend for the correlation of the sum of M+E+C scores with a higher degree of each pairwise colocalization in IgAN and IgAVN, reaching significance for C3-IgA in IgAN and IgAVN and for C3-IgG in IgAVN. CONCLUSIONS: Although immune-complex deposits differ between IgAN and IgAVN, our data support the nephritogenic role of C3-IgA-containing immune complexes in both diseases.