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Friday, January 13, 2012

TOPIC DISCUSSION: Atypical ANCA and it's significance?


Three types of positive ANCA are reported: C-ANCA, P-ANCA and atypical ANCA, based on the staining pattern of the neutrophils in the immunofluorescence assay.

C-ANCA: A coarse, clumpy, granular cytoplamic staining of neutrophils, which is usually associated with anti PR3 antibodies
P-ANCA:  A perinuclear staining pattern of neutrophils which is usually associated with anti MPO antibodies. The presence of some anti-nuclear antibodies (homogeneous ANA) may interfere with ANCA testing and invalidate the reporting of P-ANCA. In this situation, an indeterminant result is reported.  However, ANA do not usually interfere with ELISA testing.
Atypical ANCA: Patterns of neutrophil cytoplasmic and / or perinuclear fluorescence  other than the two above, which  occurs when neutrophil antigens other than MPO or PR3 are the antibody target.
Confusion arises when p-ANCA and c-ANCA are negative and so is MPO and PR3 but then you get an atypical ANCA positive. The indirect immunoflourescence (IIF) is the above test used and is not that good as the ELISA.   When the IIF and ELISA are used,  here is a specific things can arise:

1. C-ANCA positive:- suggestive of Wegener's Granulamatosis(WG), Microscopic polyangitis( MPA) or Churg Strauss(CS) - usually ELISA with MPO and PR3 is then performed to confirm
2. P-ANCA positive:- suggestive of MPA, and some times WG and CS. Again ELISA is needed.
3. Atypical ANCA positive:- Not associated with WG, MPA or CS.  Usually seen with chronic inflammation, bowel diseases and other autoimmune diseases. ELISA still needed to make sure no MPO or PR3 positivity is noted
4. ANCA negative:- Treated or inactive WG, MPA or CS. 
5. ANA positive, P-ANCA positive, C-ANCA negative:- Can be secondary due to +ANA. Again MPO and PR3 are needed
6. PR3 negative, MPO negative, +atypical ANCA:- Could be chronic infections, inflammatory bowel diseases, or autoimmune diseases ( usually not ANCA disease)
7. C-ANCA Positive, PR3- ++:- Active WG or MPA or CS
8. C-ANCA Positive, MPO ++:-Active MPA and sometimes CS or WG
9. Atypical ANCA +, PR3 +, MPO +:- Inflammatory bowel disease, doesn't occur in WG or MPA or CS
10. Atypical ANCA+, MPO+++:- Usually not seen except perhaps drug induced vasculitis

Take a look at this special article to get a more complete review of this specific testing.

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