Immune profile of IgA-dominant diffuse proliferative glomerulonephritis

Abstract

The diagnosis of IgA-dominant post-infectious glomerulonephritis (PIGN) may be challenging, as it must be differentiated from that of active IgA nephropathy. Predominant clinicopathologic features of IgA-dominant PIGN substantially overlap with those of active IgA nephropathy. Here, we present a case of a 67-year-old woman with rapidly rising serum creatinine, proteinuria and severe hypertension. The kidney biopsy findings included some features of IgA-dominant PIGN while others were more consistent with classical IgA nephropathy. We describe this patient's immune profile at the time of acute kidney injury and review the literature regarding differentiation of the two entities.

Keywords: IgA; IgA dominant post-infectious glomerulonephritis; IgA nephropathy.

Fig. 1.

Pathology features in the renal biopsy. (A) (i) Light microscopy: This glomerulus shows mild-to-moderate expansion of the mesangial matrix with mesangial hypercellularity and segmental endocapillary hypercellularity with intracapillary neutrophils (thick arrows). There are several intracapillary pseudothrombi (thin arrows). Trichrome ×600. (A) (ii) This glomerulus shows prominent glomerular basement membranes with large subendothelial eosinophilic deposits and granular mesangial deposits (arrows). Trichrome ×600. (B) Immunofluorescence microscopy. Very strong (4+) staining for IgA is shown in the mesangium and capillary loops. C3 also showed 4+ staining in the capillary loops (not illustrated). (C) (i) Electron microscopy. Numerous large electron-dense immune-complex deposits are present in the mesangium. One large hump-like subepithelial deposit (arrow) in the notch area is shown. The foot processes are completely effaced. (C) (ii) Subendothelial deposits (arrows).

Fig. 2.

Circulating IgA1-containing complexes were isolated from serum (native or IgA- or IgG-depleted) by size-exclusion chromatography on a calibrated Superose 6 column, fractions added to cultures of primary human mesangial cells, and cellular proliferation assessed by thymidine incorporation. High-molecular-mass fractions of serum induced proliferation of the mesangial cells. Fractions 26 and 30 stimulated cellular proliferation in an IgA- and IgG-dependent manner, whereas fractions 36–42 were inhibitory in an IgA-dependent manner. Fractions 30, 36 and 42 (boxed) were analyzed for total IgG and IgG subclasses (see Table 1).