ANCA-Associated Renal Diseases

1. What is ANCA?

• Antineutophil cytoplasmic antibodies

• Autoantibodies with specificity for constituents of neutrophil primary granules and monocyte lysosomes

2. Where are ANCA antigens in normal conditions and after activation of neutrophils?

• Detected in serum using IF – 2 types

• C-ANCA (cytoplasmic) – most commonly seen in Wegener’s

• P-ANCA (perinuclear) – specificity for myeloperoxidase and reacts w/ neutophil elastase, seen in renal-limited disease

• With activation of neutrophils, granules are present at surface of cells, and circulating ANCA may cause respiratory burst and degranulation

3. Know the clinical presentation of polyarteritis nodosa, Wegener’s granulomatosis, and pauci-immune necrotizing glomerulonephritis

   • Polyarteritis nodosa (PAN)
   • Mean age of onset is ~45-58 years (w/ superadded GN, it’s a little earlier)
   • Fever, myalgia, weight loss, and arthralgia are common
   • Other symptoms depend on organ systems involved
   • Main laboratory findings include plasma ANCA, elevation of C-reactive protein, positive rheumatoid factor, and circulating immune complexes
     

• Wegener’s granulomatosis (WG)

• Mean age of onset is 36-54 years

• Initial signs involve the upper airway, lung, and kidney

• Upper airways: rhinitis, sinusitis, epistaxis, deafness and ulcers

• Lung: dyspnea, cough, hemoptisis, and radiologic signs such as infiltrates, nodules, and cavitation

• Renal: oliguria, hematuria, proteinuria, and raised serum creatinine

• Renal symptoms are usually the last presenting signs, but may precede lung symptoms in some cases

• Pauci-immune necrotizing GN (PINGN)

• Renal-limited variant of systemic vasculitis
  

4. Know the vascular lesions in PAN and Wegener’s granulomatosis

• PAN

• Mainly affects arteries of arcuate size
• Acute, healing, and healed lesions may be present at same time in a specimen
• Acute lesions – whole circumference or a portion is replaced by fibrin-like material (fibrinoid necrosis) and infiltrated by neutrophils, monocytes, and eosinophils. Elastic lamina is destroyed. Cellular reaction spreads to surrounding tissue and forms a layer that may encircle the vessel. Aneurysm formation if only part of vessel wall affected.
• Healing – Inflammatory cells decrease in #, necrotic areas invaded by smooth muscle cells, which may cause intimal thickening and lumen narrowing
• Healed – No inflammatory cells, destroyed part of arterial wall replaced with fibrous tissue. Hemosiderin deposits may be present.
  

• WG

  • Necrotizing lesions seen in arterioles and interlobular arteries

  • Rarely involve arcuate arteries

  
  

5. Know the glomerular lesions in PAN, Wegener’s granulomatosis, and pauci-immune necrotizing glomerulonephritis

• PAN

• May occur w/o GN  infarcts and aneurysms seen

• Focal segmental necrotizing glomerulonephritis

• Fibrinoid necrosis associated with eosinophillic areas

• Segmental or diffuse proliferative change

• Granulomatous changes are less common than in WG

• Tubules show atrophy/necrosis

• WG

• Focal segmental necrotizing glomerulonephritis

• Mesangial hypercellularity

• Granulomatous glomerulonephritis more common

6. Know the mechanism of tissue injury in ANCA-associated disease

   • Circulating ANCA interacts with primed neutrophils to cause a respiratory burst and degranulation

   • Respiratory burst releases toxic oxygen

   • Degranulation releases lytic enzymes

Category: Pathology Notes