Anca and panca
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ANCA vasculitis classification diagnosis
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ANCA and pANCA
What is ANCA?
Anti-Neutrophil Cytoplasmic Antibody (ANCA) refers to a pattern of reactivity seen when patient serum is incubated with alcohol-fixed neutrophils (indirect immunofluorescence, IIF). These are autoantibodies directed against proteins in the cytoplasmic granules of neutrophils and monocytes.
- Harrison's Principles of Internal Medicine 22e, p. 2937
- Quick Compendium of Clinical Pathology 5e, p. 346
Two Major Patterns
| Feature | cANCA | pANCA |
|---|---|---|
| Staining pattern | Diffuse, granular cytoplasmic | Perinuclear / nuclear |
| Primary antigen | Proteinase-3 (PR3), a 29-kDa serine proteinase in azurophilic granules | Myeloperoxidase (MPO) |
| Other antigens | - | Elastase, cathepsin G, lactoferrin, lysozyme, BPI (but only anti-MPO is linked to vasculitis) |
| Key associated disease | Granulomatosis with Polyangiitis (GPA, formerly Wegener's) - >90% of active cases | Microscopic Polyangiitis (MPA), EGPA (Churg-Strauss), pauci-immune crescentic GN |
Why the pANCA pattern appears perinuclear (technical artifact)
During ethanol fixation, MPO and other strongly cationic granule components migrate from the cytoplasm to the negatively charged nuclear envelope, producing the perinuclear ring artifact. The more neutral PR3 molecule stays in the cytoplasm, giving the c-ANCA pattern. This is purely a lab artifact - in vivo, both antigens reside in azurophilic granules.
- National Kidney Foundation Primer on Kidney Diseases 8e, p. 205
ANCA-Associated Vasculitides (AAV) - (+)ANCA Diseases
The three canonical ANCA-positive small-vessel vasculitides:
- Granulomatosis with Polyangiitis (GPA) - predominantly cANCA/anti-PR3 (>90% in active disease)
- Microscopic Polyangiitis (MPA) - predominantly pANCA/anti-MPO
- Eosinophilic Granulomatosis with Polyangiitis (EGPA / Churg-Strauss) - up to 40% ANCA-positive, most typically pANCA/anti-MPO
(-) ANCA vasculitides (ANCA negative)
- IgA vasculitis (Henoch-Schonlein Purpura) - IgA deposits on IF
- Cryoglobulinemia
- Behcet's disease
- Anti-GBM disease (Goodpasture)
- Urticarial vasculitis
- Frameworks for Internal Medicine, p. 697
Disease Manifestations of AAV
| Organ | Manifestation |
|---|---|
| Nose/sinuses | Nasal crusting, saddle nose, septal perforation, sinusitis |
| Lung | Pulmonary nodules, hemorrhage, interstitial fibrosis |
| Kidney | Pauci-immune necrotizing/crescentic glomerulonephritis |
| Eye | Scleritis, episcleritis, retro-orbital pseudotumor |
| Skin | Palpable purpura, cutaneous ulcers |
| Nerves | Mononeuritis multiplex |
| Ear | Otitis media, conductive/sensorineural hearing loss |
National Kidney Foundation Primer on Kidney Diseases 8e, Table 17.1
Testing Protocol
ANCA testing uses two complementary assays:
- Indirect Immunofluorescence (IIF) on ethanol-fixed neutrophils - sensitive but not specific, especially for pANCA
- ELISA for anti-PR3 and anti-MPO antibodies - highly specific; modern high-sensitivity ELISAs now rival IIF in sensitivity
Key rule: A positive IIF result must always be confirmed with ELISA, because:
-
Antinuclear antibodies (ANA) can be mistaken for a pANCA pattern on IIF
-
"Atypical ANCs" (antibodies to cathepsin G, elastase, lactoferrin, lysozyme) produce pANCA patterns but have no vasculitis association
-
ANA interference: some ANAs (especially homogeneous pattern) on ethanol-fixed neutrophils can mimic pANCA - to exclude, ANA testing is performed on all ANCA-positive samples
-
NKF Primer on Kidney Diseases 8e, p. 205
-
Tietz Textbook of Laboratory Medicine 7e
Pathogenesis
How ANCA causes vessel damage:
In resting neutrophils, PR3 and MPO are hidden inside azurophilic granules - inaccessible to serum antibodies. Disease occurs in two steps:
- Priming: TNF-α or IL-1 causes neutrophil "priming," causing PR3/MPO to translocate to the cell surface
- Activation: ANCA binds these surface antigens, fully activating the neutrophil - leading to:
- Release of toxic oxygen radicals
- Degranulation of proteolytic enzymes
- Neutrophil-endothelium adhesion
- Vessel wall destruction
Granulomatous vasculitis also involves T-lymphocyte-mediated mechanisms - endothelial cells activated by IFN-γ express HLA class II, interact with CD4+ T cells, and secrete IL-1/TNF-α, further amplifying ELAM-1 and VCAM-1 expression.
- Harrison's Principles of Internal Medicine 22e, pp. 2937-2938
pANCA in Non-Vasculitic Conditions
A pANCA pattern not due to anti-MPO antibodies is seen in several non-vasculitic conditions:
- Inflammatory bowel disease - particularly Ulcerative Colitis (UC) and Primary Sclerosing Cholangitis (PSC)
- Rheumatic autoimmune diseases
- Certain drugs
- Infections: endocarditis, bacterial airway infections in cystic fibrosis
This is why confirmation with anti-MPO ELISA is mandatory before attributing a pANCA result to vasculitis.
Quick Memory Summary
| cANCA | pANCA | |
|---|---|---|
| Antigen | PR3 | MPO |
| Pattern | Cytoplasmic (granular) | Perinuclear (artifact of fixation) |
| Disease | GPA (Wegener's) | MPA, EGPA, Churg-Strauss |
| Also seen in | - | UC, PSC, IBD (non-vasculitic pANCA) |
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