Patologia delle vasculiti ANCA-associate

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Pubblicato il 29 aprile 2013

Pathology of the ANCA-associated vasculitides

Franco Ferrario, Alice Vanzati, Daniela Pilla, Fabio Pagni

Nefropathology Service, Dipartimento di Patologia, Ospedale San Gerardo, Università Milano Bicocca, Monza

Corrispondenza a: Franco Ferrario; Dipartimento di Patologia, Ospedale San Gerardo, Università Milano Bicocca, 20900 Monza, Italia; Tel: 0039 039 2332555; Fax 0039 039 2332548; mail: frferrario@gmail.com

Abstract

Le linee guida internazionali sottolineano il ruolo cruciale della biopsia renale nella diagnosi della glomerulonefrite da autoanticorpi anti-citoplasma dei neutrofili (Anti-Neutrophil Cytoplasmic Autoantibody: ANCA) - (Poliangite microscopica, Granulomatosi con poliangite e Granulomatosi eosinofila con poliangite).

1) In base alla recente Chapel Hill Consensus Conference del 2012, le vasculiti ANCA-associate sono classificate nel gruppo delle vasculiti con interessamento dei piccoli vasi (Small vessel vasculitis).

2) La glomerulonefrite necrotizzante extracapillare pauci-immune è la caratteristica morfologica della vasculite ANCA-associata. La lesione può variare ampiamente per quanto riguarda il grado e l'entità del danno: da necrosi segmentaria del flocculo a massive semilune circonferenziali e frequenti reazione granulomatose periglomerulari.

3) L’ANCA test è altamente specifico per questi tipi di vasculite autoimmune, ma la biopsia renale rimane ancora il gold standard per la diagnosi finale, la valutazione prognostica e l’ intervento terapeutico, tenendo anche conto della discrepanza frequente tra caratteristiche cliniche e morfologiche.

4) Le semilune del flocculo glomerulare sono caratterizzate da accumulo di Monociti-Macrofagi attraverso l’attivazione delle molecole di adesione cellulare vascolare (VCAM-I). I macrofagi attivati hanno un ruolo chiave nella progressione del danno renale cronico a causa della loro capacità di produrre sostanze direttamente coinvolte nel rimodellamento della matrice (i.e. Tumor Growth Factor b).

5) La diffusa e marcata infiltrazione interstiziale di linfociti T, B e Monociti-Macrofagi è un'altra caratteristica morfologica frequente con aspetto di tubulite recentemente considerata un marker importante di prognosi peggiore.

6) Purtroppo le alterazioni renali in follow-up a lungo termine sono in gran parte sconosciute a causa di pochissimi studi su biopsie ripetute in questi quadri patologici.

7) Malgrado uno scoring standardizzato per biopsie renali sia stato sviluppato in precedenza, una classificazione istopatologica finale è ancora carente. La Società Europea per lo studio delle vasculiti (EUVAS) ha proposto un sistema di classificazione basato sulla patologia glomerulare valutata al microscopio ottico. Questa classificazione è costruita intorno a quattro categorie: focale, crescentica, sclerotica e mista. Una correlazione preliminare con caratteristiche cliniche di 100 casi di vasculiti ANCA-associate ha dimostrato che queste categorie classificative sono state considerate al follow up gli unici fattori predittivi indipendenti per la stima del filtrato glomerulare (eGFR). L’EUVAS sta valutando un'ulteriore conferma di questa classificazione con lo studio internazionale attualmente in corso.

Abstract

The international guidelines emphasize the crucial role of renal biopsy in the diagnosis of Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)- associated glomerulonephritis (Microscopic Polyangiitis, Granulomatosis with Polyangiitis and Eosinophilic Granulomatosis with Polyangiitis).

1) According to the recent 2012 Chapel Hill Consensus Conference, ANCA- associated vasculitides are classified in the group of small vessel vasculitis.

2) Pauci-immune necrotizing crescentic glomerulonephritis is the morphological hallmark of ANCA-associated vasculitis. The lesion can vary widely in severity and extent of the damage, from segmental tuft necrosis to massive circumferential crescents and frequent peri-glomerular granulomatous reaction.

3) The ANCA test is highly specific for these types of autoimmune vasculitides but renal biopsy still remains the gold standard for final diagnosis, prognostic evaluation and therapeutic intervention, although discrepancy between clinical and morphological features is frequently found.

4) Crescentic damage of the glomerular tuft is characterized by monocyte.- macrophage accumulation through Vascular Cell Adhesion Molecule-1 (VCAM-1) activation. Activated macrophages are considered to have a key role in the chronic progression of renal damage due to their ability to produce substances directly involved in matrix remodelling (Tumor Growth Factor b).

5) Diffuse and marked interstitial infiltration of T, B lymphocytes and monocyte- macrophages is another frequent morphological feature with aspects of tubulitis recently being considered important markers for a worse prognosis.

6) Unfortunately, repeat biopsies are infrequently performed in these disorders and long-term renal changes have remained largely unidentified.

7) Despite the formulation of standardized scoring for renal biopsies, definitive histopathologic classification is still lacking. The European Vasculitis Study (EUVAS) group has proposed a classification system based on glomerular pathology as assessed by light microscopy which is, in turn, divided into four categories: focal, crescentic, sclerotic and mixed. A preliminary correlation with clinical features in 100 cases of ANCA-associated vasculitis has demonstrated that renal biopsy categories were the only independent predictors for the estimated glomerular flow rate (eGFR). The international study currently way is being evaluated by EUVAS for possible confirmation of the classification.

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Contenuti articolo

release 1
pubblicata il 29 aprile 2013
Da

Franco Ferrario, Alice Vanzati, Daniela Pilla, Fabio Pagni

Nefropathology Service, Dipartimento di Patologia, Ospedale San Gerardo, Università Milano Bicocca, Monza

Parole chiave: Biopsie ripetute, classificazione istologica, EGPA, GPA, Immunoistochimica, MPA, vasculite ANCA-associata

Key words: ANCA-associated vasculitis, EGPA_, GPA_, histological classification, immunohistochemistry, MPA_, repeated biopsies

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