1. Prepared by Dr. Anees Al-Saadi
April 2008
Clinical immunology principles and practice RICH, 2nd edition
Methodological update ANCA.mht
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2.  ANCA auto antibodies related to
inflammatory disorders.
 van der Woude et al. in 1985 showed ANCA
related to Wegener's granulomatosis.
Methodological update ANCA.mht

3.  Enzymes used in the defense against
bacteria found in WBCs granules.
 Most reactivities were found molecular
weights ≈29kD & l4OkD.
Methodological update ANCA.mht

4.  Two main enzymes in ANCA take part in the
killing of bacteria by:
 Proteinase 3 (PR3) showing cANCA pattern.
 Myeloperoxidase (MPO) showing pANCA
pattern.
Methodological update ANCA.mht

5.  Molecular weight of 29kD antigen:
 Which is proteinase .
 PR3 is a single protein chain that is glycosylated.
 Is very similar to other serine proteases like
elastase and cathepsin G.
Methodological update ANCA.mht

6.  Myeloperoxidase (MPO)
 MPO is a dimer molecular weight of l4OkD
consisting of one heavy & light chain .
 It is glycosylated with mannose oligosaccharide
chains.
 Is cleaved by heating and has a green color .
Methodological update ANCA.mht

7.  Many other antigens have been described to
be associated with ANCA,
 i.e. elastase,
 lactoferrin cathepsin G,
 BPI
 defensins, HMG1/2, catalase etc.
Methodological update ANCA.mht

8. Methodological update ANCA.mht

9.  It is poorly understood how ANCA are developed.
 Two possible mechanisms of ANCA development
are postulated:
 Theory of molecular mimicry.
 Theory of defective apoptosis.
Methodological update ANCA.mht

10.  Theory of molecular mimicry.  Theory of defective apoptosis.
 Superantigens have the  ANCA may be developed
power to stimulate a strong either via ineffective
immune response . THEY apoptosis or ineffective
have regions that resemble removal of apoptotic cell
self-antigens – this is the fragments, leading to the
theory of molecular mimicry. exposure of the immune
system to molecules
 classical example in post normally sequestered inside
group A streptococcal the cells. This theory solves
rheumatic heart the paradox of how it could
disease, where there is be possible for antibodies to
similarity between M be raised against the
proteins of Streptococcus intracellular antigenic
pyogenes to cardiac myosin targets of ANCA.[4]
and laminin.
Methodological update ANCA.mht

11. p-ANCA, show a perinuclear staining pattern
c-ANCAs, show a diffusely granular,
cytoplasmic staining pattern
Atypical that develop against antigens other than MPO or
PR3 will occasionally result in patchy staining
Methodological update ANCA.mht

12. cANCA disease :
pANCA disease association: Atypical
association
• Primary vasculitis • Primary vasculitis
• Primary
Microscopic polyangitis sclerosing
Churg-Strauss syndrome • Wegener's cholangitis
Polyarteritis nodosa granulomatosis
• Primary biliary
• Collagenosis • Microscopic cirrhosis
Felty's syndrome polyangitis
SLE • Autoimmune
Rheumatiod arthritis • Churg-Strauss hepatitis
Sjögren's syndrome syndrome.
• SLE
• Chronic inflammatory bowel
disease • RA
• Chronic liver disease
Primary sclerosing cholangitis
Methodological update ANCA.mht

13. Definition Wegener's granulomatosis is a uncommon type of
(vasculitis).
It classically involves the lungs, the nasal passages
(sinuses), and the kidneys.
Nasal or oral inflammation:
Clinical Lungs: abnormal chest X-ray .
Picture
Kidneys: with microhematuria or red cell casts
Biopsy: granulomatous inflammation
Initial treatment is corticosteroids and oral CYC.
On remission treatment is changed to azathioprine
Treatment or methotrexate.
Duration of therapy should be at least one year.

14. • Renal GN 79%.
Definition
Features
Treatment
• daily/
• May progress to
irreversible rapid intermittent
progressive renal I.v
• Microscopic damage If not cyclophosph
polyangiitis treated . amide 6-
(MPA) is • Weight loss 12months .
vasculitis of 73%.
small vessels. • Methotraxat
• Fever 55%. e or
• Pulmonary: azathioprine
alveolar in remission
stage of the
hemorrhage. disease.
Methodological update ANCA.mht

15. Definition Features Treatment
• Treatment is
• 1. A prodromal prednisone for mild
• An eosinophil- phase cases , systemic
rich form of • Allergic disease. involvement
granulomatous cyclophosphamide
inflammation • 2. Eosinophilia- to be added.
mainly tissue infiltration
involving phase: • Clinical remission
• Eosinophilia. seen in 90% of the
respiratory tract cases and
• 3. Vasculitic phase : recurrences seen in
• Asthma and 25%
• Systemic
eosinophilia. necrotizing
vasculitis .
Methodological update ANCA.mht

16.  The application of ANCA useful in both the
diagnosis and monitoring of disease activity .
Applications of Antineutrophil Cytoplasmic Antibody.mht

17. Microscopic Wegener's Churg-
Polyangiitis Granuloma Strauss
ANCA tosis Syndrome
PR3-ANCA 40 80% 10%
MPO-ANCA 50% 20% 60%
Negative 10% 5% 30%
Methodological update ANCA.mht

18. Prevalence of ANCA in renal vasculitis
Type of renal ANCA test positivity (%)
vasculitis
P-ANCA C-ANCA
Polyarteritis nodosa 10-20% 10-20%
Microscopic polyangitis 50-80% 10-20%
Wegener`s granulomatosis 10-20% 80-90%
Necrotizing and crescentic 50-80% 10-20%
GN
Clinical immunology principles and practice RICH, 2nd edition

19.  In Juvenile rheumatoid arthritis :
 Occur in 10-20% of active conditions.
 Showing atypical pattern.
 Does not correlate with clinical parameters.
Clinical immunology principles and practice RICH, 2nd edition pr

20.  Autoimmune hepatitis :
 Showing p-ANCA pattern.
 Seen in 65%-96% in AIH-1 not in AIH-2.
 Not correlated with disease activity and liver
function test.
Clinical immunology principles and practice RICH, 2nd edition pr

21.  Inflammatory bowel disease:
 Showing p-ANCA pattern more seen in UC than
CD.
 Not been used for distinguishing the 2 diseases .
Clinical immunology principles and practice RICH, 2nd edition pr

22.  Drug-induced ANCA:
 Picture of ANCA-associated vasculitis (AAV).
 Propylthiouracil is a well-documented cause of drug-
induced AAV.
 Other drugs:
▪ Hydralazine,sulfasalazine.
▪ minocycline, D-penicillamine.
▪ ciprofloxacin, phenytoin.
▪ clozapine, allopurinol, and pantoprazole.
AccessMedicine - ANCA induced by drugs.mht

23.  Usually of p-ANCA pattern.
 Slow resolving condition.
 Good responding to low dose of
immunosuppressive agents.
AccessMedicine - ANCA induced by drugs.mht

24.  Prognostic significance of ANCAs:
 Increasing ANCA titers do not reliably predict relapse.
 Nevertheless, many clinicians assume that ANCA
titers are reliable indicators of disease activity !.
ANCAClinical Applications of Antineutrophil Cytoplasmic Antibody.mht

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