Kidney Week

Abstract: PUB315

Glomerular Injury and Differences in Colocalization of Glomerular IgA, IgG, and Complement C3 in Patients with IgA Vasculitis with Nephritis

Session Information

• Publication Only

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Novak, Lea, The University of Alabama at Birmingham, Birmingham, Alabama, United States

Lea Novak, MD

• Hall, Stacy D., The University of Alabama at Birmingham, Birmingham, Alabama, United States

Stacy D. Hall, MPH

• Rizk, Dana V., The University of Alabama at Birmingham, Birmingham, Alabama, United States

Dana V. Rizk, MD

• Julian, Bruce A., The University of Alabama at Birmingham, Birmingham, Alabama, United States

Bruce A. Julian, MD

• Haas, Mark, Cedars-Sinai Medical Center, Los Angeles, California, United States

Mark Haas, MD, PhD

• Novak, Jan, The University of Alabama at Birmingham, Birmingham, Alabama, United States

Jan Novak, PhD

Background

IgA vasculitis is usually a self-limited disease but some children and adults with nephritis (IgAVN) progress to kidney failure. Routine immunofluorescence of kidney-biopsy specimens from IgAVN patients show glomerular immunodeposits with IgA as dominant or co-dominant immunoglobulin with variable staining for IgG and complement C3 (C3). The goal of this study was to assess pairwise colocalization of IgA, IgG, and C3 and correlate the data with kidney histologic findings.

Methods

Remnant frozen kidney biopsies from 23 IgAVN patients (age range 5-67 yr, mean 20.2 yr) were stained for IgA, IgG, C3, and nuclei. Using confocal microscopy, four-fluorochrome images of glomeruli in multiple optical planes were acquired for each slide. Sixty regions of interest were selected and Pearson correlation coefficient (PCC) colocalization data were generated for each IgA-C3, IgA-IgG, and IgG-C3 pairwise comparison. Mean value of PCC for each pairwise comparison for each slide was calculated and the colocalization of the pairs was evaluated. To correlate results with Oxford MEST-C scores, biopsies were divided into paired groups: M0/M1, E0/E1, S0/S1, T0/(T1+T2), and C0/(C1+C2). Differences in PCC in IgA-C3, IgA-IgG, and IgG-C3 colocalization for these paired groups were evaluated.

Results

Glomerular staining for IgA, IgG, and C3 was identified in all 23 biopsies including those without IgG on routine immunofluorescence (n=16). Immune complexes exhibited higher PCC for IgA-C3 or IgA-IgG than for IgG-C3 (P=0.002 and P=0.023, respectively). Comparison of colocalization data with MEST-C scores showed higher IgA-C3 colocalization in biopsies with endocapillary hypercellularity (E1) compared to biopsies without (E0; P=0.034). In contrast, biopsies with segmental glomerulosclerosis (S1) showed lower IgA-IgG colocalization compared to biopsies without (S0; P=0.044).

Conclusion

IgG was detected in all biopsies, including those without IgG on routine immunofluorescence. IgA, IgG, and C3 components of glomerular immunodeposits showed pairwise colocalization. Colocalization studies suggested that complement likely contributes to the kidney injury in IgAVN biopsies with endocapillary hypercellularity. In contrast, segmental glomerulosclerosis showed differences only in IgA-IgG colocalization.

Funding

• NIDDK Support