Anti-Neutrophil Cytoplasmic Antibody (Anca)

Hepatitis B is associated with polyarteritis nodosa (PAN), a necrotizing vasculitis of small- and medium-sized muscular arteries involving all organ systems.

A significant percentage of patients with PAN have hepatitis B antigenemia.

They also have circulating immune complexes containing hepatitis B antigen.

Hepatitis B antigen, IgM, and complement can be demonstrated in blood vessel walls. P-ANCA (perinuclear-anti nuclear cytoplasmic antibody) is a marker for polyarteritis nodosa.

Hepatitis A is not associated with a vasculitis. Hepatitis C accounts for 50-70% of chronic hepatitis. Chronic hepatitis C can be associated with immune-complex mediated extrahepatic complications, but is less common than hepatitis B.

Hepatitis C does have a significant association with essential mixed cryoglobulinemia, which presents with glomerulonephritis, arthralgias, hepatosplenomegaly, and lymphadenopathy, in addition to a vasculitis. However, there is no association with p-ANCA.

Hepatitis D requires that the patient be co-infected with hepatitis B. As such, it does not independently cause disease, but it can produce a worsening of the liver disease.

C-ANCAs (Cytoplasmic anti-neutrophil cytoplasmic antibodies), are a type of autoantibody formed against proteinase 3.

P-ANCA (Perinuclearanti-neutrophil cytoplasmic antibodies) are antibodies directed against myeloperoxidase.

Ref: Harrison’s Principles of Internal Medicine, 16th Edition, Page 2002; Thurlbeck’s Pathology Of The Lung, William M. Thurlbeck, 3rd Edition, Page 372; Rheumatology Secrets, Sterling G. West, 2nd Edition, Page 226.

There are two major categories of ANCA. Other statements are true.

Ans. is ‘a’ i.e., cANCA

Antineutrophil cytoplasmic antibodies (ANCA)

o ANCA are heterogenous group of autoantibodies directed against antigens which are found within the primary granules of neutrophil and in the lysosomes of monocytes and in EC’s.

o The description of these autoantibodies is based on the immunofluorescence pattern of staining of ethanol fixed neutrophils. With immunofluorescence two principal patterns are recognized:

1.  C^ytoplasmic (c-ANCA):

o This shows cytoplasmic localization of the staining and the target antigen for this type of autoantibody is — proteinase-3 (PR3), a neutrophil granule constituent.

2.  Perinuclear staining (p-ANCA)

o This shows perinuclear staining and the target antigen here is myeloperoxide (MPO).

Remember that either of these antibodies may occur in a patient with ANCA associated small vessel vasculitis but

(i) cANCA  Typically found in

• Wegener’s granulomatosis

(ii) pANCA  Typically found in

• Microscopic polyangiitis

o Churg-Strauss syndrome

o Idiopathic crescentic glomerulonephritis

o Goodpasteur’s syndrome.

o pANCA’s are also associated with certain non-vasculitic entities such as certain rheumatic and nonrheumatic autoimmune diseases, Inflammatory bowel diseases, certain drugs, • infections such as endocarditis and • bacterial airway infection in patients with cystic fibrosis.

Ans. is ‘b’ i.e., Idiopathic crecsentric glomerulonephritis

Ans. is ‘c’ i.e., Wegener’s granulomatosis

Ans. is ‘a’ i.e., Churg-strauss syndrome; ‘c’ i.e., Wegener granulomatosis

Ans. is ‘a’ i.e., Good pasture syndrome; ‘b’ i.e., Wegner’s granulomatosis

Amongst the given options two are associated with ANCA: Wegner’s granulomatosis is positive for cANCA and goodpasture syndrome is positive for pANCA.

Ans. is ‘c’ i.e., Wegener’s granulomatosis

o Renal and pulmonary symptoms with positive c-ANCA suggest the diagnosis of wegener’s glomerulonephritis (see above explanation).

o Clinical syndrome of wegener granulomatosis may be very similar to classical PAN or microscopic polyangitis. Following facts will help you to differentiate wegner granulomatosis from other Two ‑

Wegeners granulomatosis Vs classical PAN

o Wegener’s granulomatosis involves small vessels (arteriole, venule, capillary), while PAN involves medium size vessels.

o Wegener’s granulomatosis is associated with c-ANCA, while classical PAN is not associated with ANCA. o In wegener’s granulomatosis there is lung involvement, but not in classical PAN.

o In wegener’s granulomatosis there is glomerulonephritis (hematuria) without hypertension, while in classical PAN there is hypertension without glomerulonephritis.

o In wegener’s granulomatosis, there is granuloma formation, while it is absent in classical PAN. o Classical PAN shows microaneurysms which are absent in wegener’s granulomatosis.

Wegner’s granulomatosis Vs microscopic polyangitis

o Wegener’s granulomatosis is associated with c-ANCA, while MPA is associated with p-ANCA. o Granuloma formation occurs in wegener’s granulomatosis, not in MPA.

o Lung cavities and nodules are seen in wegener’s granulomatosis, but not in MPA.

Ans. is ‘b’ i.e., Polyarteritis Nodosa

Ans. is ‘c’ i.e., Seen in Henoch Schonlein purpura

Answer is A (Ulcerative Colitis)

Presence of mucus and blood in stool along with positive ANCA antibodies suggests a diagnosis of ulcerative colitis

Different Clinical, Endoscopic and Radiographic Features

Answer is A (Goodpasture’s syndrome)

• Association of hematuria and hemoptysis suggest a diagnosis of Goodpasture’s syndrome.

Goodpasture’s syndrome and ANCA

1. ANCA is typically negative in Goodpastures syndrome and it is classified as an ANCA negative vasculitis

Nevertheless

• ANCA seropositivity may occur in upto 30 percent of patients with Goodpasture’s.syndrome.
• These patients with ANCA have subtle signs of a systemic vasculitis and represent an overlap between goodpastures and either Wegener’s granulomatosis (WG) or Microscopic polyangitis(MPA)-Current Diagnosis and Treatment in Pulmonary Medicine

Answer is D (Takayasu Arteritis):

Takayasu Arteritis is not associated with ANCA

Note:

If p-ANCA is not against Myeloperoxidase (or CANCA is not against Proteinase-3), look for causes other than Vasculitis for the positive ANCA.

Answer is D (Good pasture’s syndrome):

Goodpasture’s syndrome is not classified as an ANCA positive vasculitis.

Answer is B (Henoch Schonlein Purpura):

Henoch Schonlein Purpura is an ANCA Negative Vasculitis

Answer is B (H.S. Purpura) :

H.S. purpura is not associated with any antinuclear cytoplasmic antibody (ANCA). It is an example of ANCA negative vasculitis.

• ANCA (Antineutrophilic cytoplasmic Antibodies) arc Antibodies directed against certain proteins in cytoplasmic granules of Neutrophil & monocytes.
• These are two major categories of ANCA based on different targets for the antibodies.

ANCA (Antineutrophic cytoplasmic antibodies):

ANCA is of 2 types

C-ANCA

(Cytoplasmic proteinase 3^q is the target antigen)

Wegeners Granulomatosis^q (90-95%)

P-ANCA

(perinuclear myeloperoxidase^Q is the major target antigen)

• Microscopic PAN (microscopic polyangitis)
• Churg-Strauss syndrome
• Crescenteric glomerulonephritise
• Good pasteur’s syndrome

Answer is B (Wegener’s granulomatosis):

CANCA refers to Cytoplasmic Antineutrophilic cytoplasmic antibodies and its presence is highly specific for Wegener’s granulomatosis

Answer is D (Wegener’s granulomatosis) :

Antineutrophilic cytoplasmic antibody directed against cytoplasmic proteinase-3 (cANCA) is found in 90-95% if patients with Wegener’s granulomatosis.

Answer is A (Wegener’s Granulomatosis):

cANCA refers to Cytoplasmic Antineutrophilic Cytoplasmic Antibodies and its presence is highly specific for Wegener’s Granulomatosis. Antineutrophilic Cytoplasmic Antibody directed against cytoplasmic^. proteinase-3 (cANCA) is found in 90-95% if patients with Wegener’s Granulomatosis.

Answer is A (Proteinase 3):

Proteinase – 3 (a 29 – kDA serine proteinase) present in neutrophil azurophilic granules is the major c-ANCA antigen.

Major c-ANCA antigen        Proteinase 3 (PR-3)

Major p – ANCA antigen    Myeloperoxidase (MPO)

Answer is B (Microscopic polyangitis) :

PAN can broadly be classified into

Classic PAN
(now referred to an PAN)

• Classified as Medium Vessel Vasculitis
• Necrotizing inflammation of small & medium sized arteries.
• No involvement of capillaries & venules
• Pulmonary vasculature is not involved.
• ANCA mostly negative (Rarely p-ANCA may be seen)

Microscopic PAN
(now called microscopic polyangitis)

• Classified as small vessel vasculitis
• Necrotizing inflammation of small & medium sized arteries.
• Capillaries & venules are involved
• Pulmonary vasculature is involved.
• ANCA positive (p-ANCA)

Ans. A: Affects large size blood vessels

Wegener’s granulomatosis is a form of vasculitis that affects the lungs, kidneys and other organs.

Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression.

Wegener’s granulomatosis is part of a larger group of vasculitic syndromes, all of which feature an autoimmune attack by an abnormal type of circulating antibody termed ANCAs (antineutrophil cytoplasmic antibodies) against small and medium-size blood vessels.

Apart from Wegener’s, this category includes Churg-Strauss syndrome and microscopic polyangiitis.

Cytoplasmic staining ANCAs that react with the enzyme proteinase 3 (cANCA) in neutrophils are associated with Wegener’s (upto 95% of cases).

If the patient has renal failure or cutaneous vasculitis, these are the most logical organs to obtain a biopsy from.

On histopathological examination, a biopsy will show leukocytoclastic vasculitis with necrotic changes and granulomatous inflammation on microscopy. These granulomas are the main reason for the appellation of “Wegener’s granulomatosis”, although it is not an essential feature.

Ans. is ‘a’ i.e., cANCA

Ans. is ‘b’ i.e., Idiopathic cresentic glomerulonephritis

Ans. is ‘a’ i.e., Wegener’s granulomatosis