This document discusses antineutrophil cytoplasmic antibodies (ANCA). It notes that ANCA are autoantibodies related to inflammatory disorders and were first associated with Wegener's granulomatosis in 1985. The two main ANCA antigens are proteinase 3 and myeloperoxidase. ANCA testing can aid in diagnosing and monitoring ANCA-associated vasculitis conditions. However, increasing ANCA titers do not reliably predict disease relapses.

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 disease, the paradox of how it could
where there is similarity be possible for antibodies to
between M proteins of be raised against the
Streptococcus pyogenes to intracellular antigenic
cardiac myosin and laminin. targets of ANCA.[4]
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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