Clinical Pathology - Anca's

Front 1

Most common test for ANCA detection are __ and ___, with __ being the most sensitive.

Back 1

- IFM (indirect fluorescence microscopy) and ELISA
- IFM is the most sensitive test for ANCA detection

Front 2

IFM detection of ANCA involves the use of __ as substrate

Back 2

- normal human neutrophils fixed to glass slides or microwell glass slides
- incubated with patient serum
- recommended that a polyspecific antihuman Ig fluorescin-labeled conjugate be used in order to detect both IgM and IgA c-ANCA too

Front 3

When interpreting c-ANCA staining, you must differentiate positive from ___

Back 3

- nonspecific cytoplasmic staining due to other autoantibodies!!
CRITERIA for nonspecific staining:
- lack of central accentuation between nuclear lobes
- <95% of neutrophils show cytoplasmic staining
- non-neutrophil specificity (staining lymphocytes; true ANCA should NOT stain lymphs)
- heterogeneous cytoplasmic granularity (should be finely granular)

Front 4

Three possible patterns seen when interpreting ANCA by IFM

Back 4

- c-ANCA
- p-ANCA
- atypical patterns

Front 5

p-ANCA pattern seen on IFM is due to __

Back 5

- perinuclear staining due to redistribution of the target antigen in the human neutrophils (substrate) after fixation in ethanol
- if fixed in formalin, the target antigen is immobilized in the cytoplasm and results in cytoplasmic staining pattern

Front 6

Can you see nuclear staining with a p-ANCA?

Back 6

- it should be perinuclear, but when high titer, there can be some nuclear staining too, mimicking an ANA

Front 7

p-ANCA and c-ANCA antigen specificity

Back 7

p-ANCA
- in vasculitis it is usually an autoAb against myeloperoxidase (MPO-ANCA)
- NOTE: many p-ANCA have specificity to other neutrophil cytoplasmic enzymes

c-ANCA
- proteinase-3 (PR-3) found in azurophilic granules of neutrophils and peroxidase-positive lysosomes of monocytes

Front 8

ANCA IFM patterns should be followed by ___

Back 8

confirmatory test
- test more specific for PR-3 and MPO

Front 9

PR-3 ELISA show __ correlation with c-ANCA pattern detection by IFM

MPO-ANCA ELISA show __ correlation with p-ANCA pattern detection by IFM

Back 9

PR-3 ELISA show GOOD correlation with c-ANCA pattern detection by IFM


MPO-ANCA ELISA show POOR correlation with p-ANCA pattern detection by IFM
- the p-ANCA pattern can be due to other autoAb (granulcyte-specific ANA, antineutrophil elastase, ANA..)

Front 10

PR-3 ANCA is detected in __% of pt w/ active Wegener's granulomatosis, while MPO-ANCA is detected in __%

Back 10

- PR-3 ANCA (c-ANCA) (70-80%)
- MPO-ANCA (p-ANCA) (<10%)

Front 11

80-90% of pts with microscopic polyangitis have ___ANCA's

Back 11

- PR-3 ANCA (c-ANCA) (30%)
- MPO-ANCA (p-ANCA) (60%)

Front 12

ANCA characteristically seen with these vasculitides __

Back 12

Wegener's granulomatosis
- PR-3 ANCA (c-ANCA) (70-80%)
- MPO-ANCA (p-ANCA) (<10%)

microscopic polyangitis
- PR-3 ANCA (c-ANCA) (30%)
- MPO-ANCA (p-ANCA) (60%)

Churg-Strauss syndrome
- MPO-ANCA (p-ANCA) (50-80%)

pauci-immune GN
- MPO-ANCA (p-ANCA) (50-80%)
- rarely PR-3 ANCA(c-ANCA)

Note: WG is the only one in which c-ANCA is the most frequent type

Front 13

ANCA associated with inflammatory bowel disease and hepatobiliary disease

Back 13

p-ANCA!! (NOTE: the specificities are not fully defined in these cases!!)

- ulcerative colitis and PSC(75-80%)
- Crohn's disease (20%)
- primary biliary cirrhosis (30%)

- primary sclerosing cholangitis (

Front 14

Most adults with UC, have p-ANCA that is sensitive to ___

Back 14

DNAse
- can be useful in distinguishing from p-ANCA seen in other conditions such as AIH and PSC

Front 15

ANCA can be seen with drug-induced vasculitides too!!

Back 15

- hydralazine - MPO-ANCA
- propylthiouracil - +ANCA

Front 16

PR-3 ANCA is most often seen in _

Back 16

WG or PAN, but can be seen in some idiopathic cresecentic GN and Churg-Strauss

Front 17

Serologic testing for __ should be performed in all pts with PAN

Back 17

- HCV, HBV, and HIV

Front 18

Polyarteritis nodosa - histology

Back 18

- focal but panmural necrotizing arteritis of small and medium-sized muscular arteries
- preferentially involves BRANCH POINTS
- inflammatory infiltrate is mixed
- circumferential or segmental necrotizing mixed inflammation with fibrinoid necrosis (HALLMARK)
- characteristically see normal segments of artery adjacent to abnormal segments

Front 19

diagnosis of PAN is made by __

Back 19

- biopsy and/or angiography

Front 20

PAN: mortality usually due to __

Back 20

- infection (complication of therapy - steroids)
- sequelae of vascular involvement (MI, stroke)

Front 21

Most cases of PAN are __, however a minority of cases are cause by___

Back 21

- most are idiopathic

- Hepatitis B causes a minority of cases of PAN. With the availability of hepatitis B vaccine now, cases of PAN caused by hepatitis B are now rare in the developed world.