Review
Figure 3 Full house IF-pattern in a renal biopsy with lupus nephritis class II. There is full house positivity for IgA (A), IgG (B), IgM (C), C3 (D), C1q (E) and light chains (kappa (F); lambda (G)). All stainings show mesangial pattern but in varying intensities. IF, immunofluorescence.
of the glomerular damage. It is perhaps also because LN involves so many different autoantibodies and immune complexes acting together that a huge variety of glomerular lesions are encoun- tered. 10 11 Some of these have a very close relation to light glomerulonephritis with mesangial staining for IgA (A); membranous nephropathy (as seen in lupus class V) with granular staining along the GBM for IgG (B); chunky deposits of IgM signifying cryoglobulins in cryoglobulinaemic glomerulonephritis (C); linear staining for IgG in anti- GBM disease (D); virtually negative staining for C3 in pauci-immune GN (E). GBM, glomerular basement membrane; GN, glomerulonephritis; ICGN, immune-complex glomerulonephritis. Figure 1 Combination of localisation patterns in immunohistochemical stainings for immunoglobulins and complement is characteristic for certain ICGN. From left to right: IgAN/IgA
microscopic lesions, for instance, wire loops (figure 2F) and pseudothrombi that are almost synonymous with the subendo- thelial deposits themselves. A recent histopathologic subclassifi- cation indicated that the majority of global class IV LN present with a membranoproliferative glomerulonephritis (MPGN)-like pattern reflected by presence of global endocapillary hypercel- lularity, wire loops and double contours, while class III LN is characterised by segmental endocapillary hypercellularity and thus resembles a vasculitis-like pattern. 12 Membranous LN (class V, IF pattern shown in figure 1B) is characterised by subepithelial
Figure 2 Light microscopic lesions may look fairly identical in different renal diseases. Knowledge on the true nature of the deposits in combination with their role in pathogenetic mechanisms that is partly dependent on their location helps to diagnose the diseases that we focus on in this review. Mesangial hypercellularity in IgA nephropathy (A) and lupus nephritis class II (B): lesions are similar by light microscopy and caused by deposits in mesangial areas. The true nature of the deposits is, however, different in the two diseases. Necrotising glomerulonephritis with crescent formation in AAGN (C) and lupus nephritis class III (D): lesions are similar by light microscopy, but are caused by subendothelial deposits in lupus nephritis whereas in AAGN, a class II hypersensitivity reaction driven by ANCA is initiating the inflammatory response leading to disruption of the glomerular basement membrane and release of cytokines into Bowman’s space giving rise to crescent formation. Wire loops in lupus nephritis class IV (E) are formed by massive subendothelial deposits. Cryoglobulins deposit at the same site, although they more often organise in nodular formations that are known as pseudothrombi (F). Only by EM, their true nature is further identified. AAGN, ANCA-associated glomerulonephritis; ANCA, anti-neutrophil cytoplasmic antibody; EM, electron microscopy.
Figure 4 Location of deposits in capillary loop correlates strongly with clinical symptoms. Red cells: mesangium; dark green cells: podocytes; yellow cells: endothelium; deposits in black. Drawings of figures by Professor Charles Jennette. Presenting features (haematuria, proteinuria and reduced kidney function) depend on the location of deposits (A). All three features, endocapillary deposits, subepithelial deposits and mesangial deposits, are encountered in lupus nephritis (B).
Kronbichler A, et al . Ann Rheum Dis 2023; 82 :585–593. doi:10.1136/annrheumdis-2022-222495
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