The distribution of IgG subclass deposition on renal tissues from patients with anti-glomerular basement membrane disease

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.

Monoclonal IgG1κ Anti–Glomerular Basement Membrane Disease: A Case Report

“…4,15,16 Other case reports of monoclonal antibody-associated anti-GBM disease have involved IgA, IgM, or l light chain only. [17][18][19] Our case is the first report of anti-GBM disease with linear GBM staining for monoclonal IgG.…”

Pathological implications of linear immunoglobulin G staining on the glomerular capillary walls in a case of infection‐related glomerulonephritis

“…Analysis of IgG subclass reported that linear IgG staining in the GBM in diabetic kidneys was restricted to IgG4; and IgG1, IgG2, and IgG3 were not detected . In anti‐GBM disease, all four IgG subclasses with dominant staining of IgG3 were present in a linear pattern in the GBM . Our case showed IgG1, IgG2, and IgG4, without IgG3, suggesting the existence of specific antibodies other than anti‐GBM antibodies.…”

“…10 In anti-GBM disease, all four IgG subclasses with dominant staining of IgG3 were present in a linear pattern in the GBM. 11 Our case showed IgG1, IgG2, and IgG4, without IgG3, suggesting the existence of specific antibodies other than anti-GBM antibodies. Although indirect immunofluorescence microscopy is not sensitive enough for adequate serologic tests for the antibodies, our finding did not support that our patient's serum at the time of biopsy contained IgG or IgG immune complex which can bind to GCW.…”

Diagnostic and management challenges in Goodpasture’s (anti-glomerular basement membrane) disease

“…IgG1 subclasses are predominantly detected by commercial methods but four subclasses of human IgG exist according to their heavy chains (IgG1, IgG2, IgG3 and IgG4) and each can bind to the GBM (14,15). IgG1 and IgG3 subclass restriction is most frequently found in patients both in sera and glomeruli and is more closely associated with disease severity; IgG3 has the greatest ability to activate complement and both IgG1 and IgG3 have the greatest affinity for binding Fc receptors (15,16).…”

“…IgG1 and IgG3 subclass restriction is most frequently found in patients both in sera and glomeruli and is more closely associated with disease severity; IgG3 has the greatest ability to activate complement and both IgG1 and IgG3 have the greatest affinity for binding Fc receptors (15,16). However, IgG4 subclass antibodies have also been found to be pathogenic both in isolation and co-existing with other immunoglobulin subclasses in atypical anti-GBM disease and are not detected by standard ELISA (14,17). Additionally, IgA anti-GBM antibodies are also not detected by standard methods and have been shown to bind various α(IV)chains (including 1,2,5 and 6) (18,19), which may not be represented in standard assays using 3(IV) (Figure 1 ).…”