Anti-Neutrophil Cytoplasmic Antibodies
(ANCA)
Ted Brown
CP Case Conference
February 24, 2012
ANCA
Antibodies against
neutrophil cytoplasmic
antigens
Most common targeted
antigens are
myeloperoxidase (MPO)
and proteinase 3 (PR3)
Prevalent among adults in
50s and 60s, M=F
We perform 2 assays:
1. Indirect
immunofluorescence
assay: normal human
neutrophils (sensitive)
2. Enzyme-linked
immunosorbent assay:
specific antigen
(specific)
When is ANCA testing ordered?
Clinical suspicion of systemic
autoimmune vasculitis
Integrate clinical and
laboratory info
Symptoms nonspecific in
early disease (fever, fatigue,
aches) to more diffuse in
later disease (proteinuria,
cough, rash/granuloma,
runny nose, peripheral
neuropathy, pulmonary
hemorrhage and
hemoptysis)
ANCA, ANA, complement,
cryoglobulins, hepatitis B
and C, rheumatoid factor,
azotemia, hematuria,
proteinuria, recent drug
history
Indirect Immunofluorescence
Patient sera on ethanol fixed PMNs
Indirect Immunofluorescence
Patient sera on ethanol fixed PMNs
Indirect Immunofluorescence
Patient sera on formalin fixed PMNs
ELISA
If indirect immunofluorescence microscopy positive,
perform ELISA
Determine amount of antibody present: Titer
determined by serial dilutions
PR3 and MPO antibodies
Diseases with ANCA
C-ANCA and PR3:
Wegener’s (90% in active,
generalized
granulomatous and
polyangiitis disease; 6070% in no active disease)
P-ANCA and MPO:
Microscopic polyangitis
(70%), Churg –Strauss
(50%), drugs
ANCA-positivity also seen
in other diseases,
including gastrointestinal
disorders
• 60-80% with ulcerative
colitis and related
disorder primary
sclerosing cholangitis
• <30% in Chron’s disease
Patient Case
48 year old female with known leukocytoclastic
vasculitis and ulcerative colitis
Recent use of cocaine
Increased arthralgias
No history of ANCA testing
Cocaine and ANCA vasculitis
~70% of cocaine bought
illicitly in US contaminated
with levamisole
Levamisole-contaiminated
cocaine associated with
ANCA vasculitis
Clinical symptoms:
arthralgias, skin lesions,
fever.
Clinical Applications of ANCA testing
Positive test really a true
positive?
Need for a tissue biopsy?
Negative test a true negative?
Controversial: reasonable
attempts should be made to
obtain histologic proof due to
long-term treatment
commitment with toxic
medications.
Clinical presentation key
Use of titers?
+ Immunofluorescence and
ELISA= PPV increased to 88%
Do not use as sole parameter
to guide therapy.