Abstract

BackgroundRenal injury of anti-glomerular basement membrane (GBM) disease is defined by the linear deposition of IgG along GBM and rapidly progressive glomerulonephritis. To date, the distribution of anti-GBM IgG subclasses on renal tissue is still unclear. In the current study, we investigated the deposition of the four IgG subclasses using immunohistochemistry in the renal biopsy specimens from 46 patients with anti-GBM disease.ResultsAll four IgG subclasses can be detected within the GBM. Anti-GBM IgG3 was detected in all patients (100%), with 39 (84.8%) patients presenting with weak segmental staining and 7 (15.2%) patients with strong linear deposition. Anti-GBM IgG2 was detected in 22 (47.8%) patients, with 20 (90.9%) patients having weak segmental deposition and 2 (9.1%) patients presenting strong linear staining. Anti-GBM IgG1 and IgG4 were detected in 9 (19.6%) and 7 (15.2%) patients, respectively. IgG deposition along tubular basement membrane (TBM) was also detected in 31 (67.4%) patients. Among them, the IgG subclass distribution was similar to that of the deposition within the GBM: IgG1 6.5% (2/31), IgG2 45.2% (14/31), IgG3 100% (31/31) and IgG4 9.7% (3/31). We observed increased inflammatory cell infiltration into the interstitium in patients with increased anti-TBM IgG3 deposits (P=0.031).ConclusionsAnti-GBM IgG3 predominantly deposits along GBM and TBM on renal biopsy specimens from patients with anti-GBM disease, which may be involved in the development of renal injury of the disease.

Highlights

  • Renal injury of anti-glomerular basement membrane (GBM) disease is defined by the linear deposition of immunoglobulin G (IgG) along GBM and rapidly progressive glomerulonephritis

  • We found that the patients with strong linear staining of IgG3 along GBM presented with lower prevalence of gross hematuria (0% vs. 38.5%, P=0.046), higher level of hemoglobin (105.1±25.8 vs. 82.0±24.9 g/L, P=0.038), and lower level of serum creatinine (445.4±333.0 vs. 779.4±367.4 μmol/L, P=0.028), compared with those with weak staining of IgG3

  • In the current study, we examined the distribution of IgG subclass deposition along GBM and tubular basement membrane (TBM) on renal biopsy specimens from a large cohort of 46 patients with anti-GBM disease

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Summary

Introduction

Renal injury of anti-glomerular basement membrane (GBM) disease is defined by the linear deposition of IgG along GBM and rapidly progressive glomerulonephritis. We investigated the deposition of the four IgG subclasses using immunohistochemistry in the renal biopsy specimens from 46 patients with anti-GBM disease. Our recent studies showed that during the initiation and progression of anti-GBM glomerulonephritis, there is an attendant increase of frequencies of anti-GBM IgG1 and IgG3 [6]. This correlation highlights the pathogenic role of IgG1 and IgG3 in the development of renal injury. In human anti-GBM disease, IgG subclass distribution along GBM has not been clearly elucidated, and their association with disease severity remains elusive

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