Antiglomerular basement membrane (anti-GBM) disease with clinical and histological features that bridge the typical to atypical spectrum

Abstract

We describe antiglomerular basement membrane (anti-GBM) disease with rapidly progressive glomerulonephritis and concurrent parainfluenza pneumonia. Circulating anti-GBM antibodies were barely detectable and disappeared rapidly following corticosteroids, cyclophosphamide and plasma exchange. Kidney biopsy demonstrated strong linear GBM staining for IgG and IgG4 and unusually prominent endocapillary hypercellularity, suggesting 'atypical anti-GBM disease', although glomerular necrosis and crescents were also seen. When kidney function deteriorated further, despite persistently absent circulating anti-GBM antibodies, a repeat kidney biopsy was performed, showing crescents in 100% of glomeruli with ongoing endocapillary hypercellularity and strong IgG and IgG4 GBM staining. This case highlights complexities in the diagnosis of anti-GBM disease, with clinical and histological features bridging the atypical to typical anti-GBM disease spectrum. We hypothesise that these findings might be explained by the presence of IgG4 (rather than traditional IgG1 or IgG3) autoantibodies. To our knowledge, this is also the first report of parainfluenza associated with anti-GBM disease.

Keywords: immunology; renal medicine.

Figure 1

Timeline of patient’s clinical course, including treatments received. GBM, glomerular basement membrane; PLEX, plasma exchange.

Figure 2

Histological features identified by kidney biopsy. (A) First biopsy: light microscopy (methenamine silver stain) showing global endocapillary hypercellularity and focal disruption to Bowman’s capsule (black arrow). (B) First biopsy: light microscopy (methenamine silver stain) the lower glomerulus contains a cellular crescent (black arrow) and segmental endocapillary hypercellularity (open arrow), in contrast to the uninvolved glomerulus above. (C) Second biopsy: light microscopy (methenamine silver stain) showing a cellular crescent (black arrow) with global endocapillary hypercellularity.(D), (E) Second biopsy: immunofluorescence with strong global linear positivity for IgG4 and IgG along the glomerular basement membrane. Findings were similar for the first biopsy (not shown). (F) Second biopsy: electron microscopy showing endocapillary hypercellularity with extensive foot process effacement (black arrow) and focal microvillous transformation (open arrow) without electron dense immune-type deposits. Findings were similar for the first biopsy (not shown).