RENAL PATHOLOGY LEARNING

Anti-GMB antibody disease

by

Franco Ferrario and Maria Pia Rastaldi

Dr Franco Ferrario
Renal Immunopathology Center
San Carlo Borromeo Hospital and Fondazione D'Amico per la ricerca sulle malattie renali
Milan, Italy

 

The main diagnostic feature of anti-glomerular basement membrane (anti-GBM) antibody disease is represented by the immunofluorescence pattern of intense and diffuse linear IgG deposition along the glomerular basement membrane. Several histological patterns can be observed by light microscopy.

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In very rare cases, glomeruli are normal or show mild mesangial proliferation. 

 

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Segmental necrotizing lesions of the glomerular tuft, without extracapillary proliferation, can be seen, as the probable expression of an early phase of the disease.

 

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The most frequent picture is a necrotizing-extracapillary glomerulonephritis, similar to ANCA-associated vasculitis, HS nephritis, necrotizing IgA GN.

 

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A massive and diffuse necrotizing-extracapillary nephritis is usually present in patients with rapidly progressive renal failure.

 

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In anti-GBM nephritis, the morphogenesis of lesions looks similar to that of ANCA-associated vasculitis, HS nephritis and necrotizing IgA GN. Indeed, most cells in the crescent are monocyte-macrophages (CD68 positive cells).

 

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Cytokeratin (CK) staining shows the mild, when not absent, participation of epithelial cells. 

 

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VCAM-1 adhesion molecule seems to be mainly involved in monocyte recruitment. 

 

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Interstitial leukocyte infiltration is often massive, mainly periglomerular and near ruptures of the Bowman's capsule. 

 

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Both quantity and location of the inflammatory cells are clearly detected by immunohistochemistry. 

 

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Glomerular granuloma-like reactions, similar to those found in ANCA-associated vasculitis, are frequently observed. 

 

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Multinucleated giant cells can be easily detected in these granuloma-like lesions. 

 

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Late biopsies are mainly characterized by glomerular sclerosis. When focal and segmental, glomerulosclerosis has the typical appearance of a well-delineated area with adhesion to the Bowman's capsule, suggesting a reparative process of the necrotizing extracapillary lesion.

 

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Small and medium sized arteritis has rarely been described, and is characterized by vessel wall necrosis and intra- and peri-vascular leukocyte infiltration. Differential diagnosis has to be made from ANCA-associated vasculitis, HS nephritis, cryoglobulinemic nephritis and rare cases of lupus nephritis.

 

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Typically, a linear IgG deposition along the glomerular basement membrane is revealed by immunofluorescence. 

 

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A more irregular and segmental linear IgG deposition characterizes the glomeruli with tuft necrosis. 

 

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Fibrin positivity is invariably found on cellular crescents. 

 

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Focal or diffuse linear IgG deposition can be found on tubular basement membranes as well. 

 

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Electron microscopy, although not essential for diagnosis, can highlight gross alterations of the glomerular capillaries and confirm the clearance of electron dense deposits.

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QUESTIONS

 

 

REFERENCES
1. Fischer EG, Lager DJ. Anti-glomerular basement membrane glomerulonephritis: a morphological study of 80 cases. Am J Clin Pathol 2006 Mar; 125(3):445-50.
2. Cui Z, Zhao MH, Xin G, Wang HY. Characteristics and prognosis of Chinese patients with anti-glomerular basement membrane disease. Nephron Clin Pract 2005; 99(2):c49-55. Epub 2004 Dec. 30.
3. Levy JB, Hammad T, Coulthart A, Dougan T, Pusey CD. Clinical features and outcomes of patients with both ANCA and anti-GBM antibodies. Kidney Int. 2004 Oct; 66(4):1535-40.
4. Cui Z, Wang HY, Zhao MH. Natural autoantibodies against glomerular basement membrane exist in normal human sera. Kidney Int. 2006 Mar;69(5):894-9.
5. O’Riordan A, Keogh JA, Watson A. Pulmonary renal syndrome due to anti-GBM and IgM C-ANCA disease requiring the use of novel therapeutic agents. Ren Fail, 2005; 27(6):791-4.
6. Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann Intern Med. 2001 Jun 5;134(11):1033-42.
7. Dalt C, Conlon PJ, Medwar W, Walshe JJ. Characteristics and outcome of anti-glomerular basement membrane disease: a single-center experience. Ren Fail, 1996 Jan, 18(1):105-12.