12.5 ANCA-Associated Vasculitis

Question 1

What is ANCA?

Answer 1

• Antibody to neutrophil cytoplasmic antigen
• NCA is a self antigen, meaning ANCA antibodies are autoantibodies

Question 2

What is ANCA associated vasculitis (AAV)?

Answer 2

Systemic, multi-organ small vessel necrotizing vasculitis with the finding of antibody to neutrophil cytoplasmic antigen

Question 3

Describe the epidemiology of ANCA associated vasculitis

Answer 3

• More common in caucasians compared to asians
• 60-70s most common age range

Question 4

ANCA associated vasculitis common clinical features

Answer 4

• Systemic symptoms (weight loss and severe lethargy) almost universal
• Anaemia of chronic disease, myalgia, arthralgia, sinusitis, fever, haemoptysis, AKI, glomerulonephritis (haematuria/proteinuria)

Question 5

What pathological findings do we suspect on renal biopsy in ANCA associated vasculitis?

Answer 5

• Pauci-immune crescentic glomerulonephritis
• Pauci-immune = few/no immune cells on immunofluorescence
• Crescentic is always a sign of severe GN

Question 6

How does the body lose tolerance to ANCA, causing AAV?

Answer 6

We don’t know

Question 7

True or false: an individual w/ ANCA antibodies will always have AAV. Call renal straight away, since this is life-threatening

Answer 7

• False
• It is life threatening, but ANCA doesn’t always guarantee AAV
• It is thought that there must be a “second hit”, such as infection, that primes certain surface proteins on neutrophils, allowing autoimmune rxn to occur

Question 8

How does ANCA associated neutrophil death cause vasculitis?

Answer 8

• Degranulation of neutrophils releases lytic enzymes
• ROS are also released, further causing endothelial cell death

Question 9

True or false: complement pathways have been shown to play a role in AAV downstream of ANCA binding to neutrophils.

Answer 9

• True
• This is exciting, because it allows us to experiment w/ complement inhibitors

Question 10

What are 2 ways we test for ANCA associated vasculitis, and their relative roles?

Answer 10

1. Indirect immunofluorescence (labeled antibody binds to ANCA, compared to control cells). This tells us it’s bound to an antigen, but we don’t know which of the two.
2. ELISA, testing for binding to both PR3 and MPO

Question 11

What are the two antigens that are thought to be implicated (one or the other in any given patient) in ANCA associated vasculitis?

Answer 11

• PR3
• MPO

Question 12

What treatments are used for ANCA associated vasculitis in the induction/maintenance phases?

Answer 12

Induction: pred + cyclophosphamide (alkylating agent) or rituximab
Mtainenance: pred + azathioprine (alylating) or mycophenolate mofeti