Vasculitis and anti-GBM associated Diseases

PR 3 Antibodies | MPO Antibodies | GBM Antibodies

 

PR 3 Antibodies

Product Article No. No. of test
EliA PR3 S (sensitive)  NEW! 14-5536-01 4x12 tests
Varelisa PR3 ANCA 177 96 96 tests

Promotion Material

Performance Folders
EliA PR3 S, MPO S (pdf)
EliA PR3, MPO, GBM (pdf)
Varelisa ANCA (pdf)

Antigens

Antineutrophil cytoplasmic antibodies (ANCA) can be subdivided in cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA). The main antigen for the cANCA reactivity is the enzyme proteinase 3 (PR3).

PR3 is a cationic protein consisting of 228 amino acids residues and belonging to the trypsin family of serine proteases. Expressed only in primates and humans, PR3 has different functions, including proteolysis of elastin, hemoglobin, fibronectin, laminin and collagen type IV, antimicrobial activities etc.

PR3 in Phadia assays is purified from human neutrophils. 

In EliA PR3 S (sensitive) the antigen is coated to the wells with an anchor technique which increases the sensitivity of the test substantially.

Disease association, antibody prevalence and specificity

  • Wegener's Granulomatosis (dependent on disease activity: about 50% in inactive disease, nearly 100% in the active generalization phase of WG), specificity >95% 
  • Microscopic Polyangiitis (small percentage) 
  • Churg-Strauss Syndrome (10-30%) 
  • Polyarteritis Nodosa (8-10%).  
  • Idiopathic Crescentic Glomerulonephritis (30%)

More information about the diseases

In general, anti-MPO and anti-PR3 do not occur in the same patient concurrently. The detection of c-ANCA with clear PR3 activity is 99% specific for necrotizing small vessel vasculitis.

When is the measurement recommended?

  • Suspicion of idiopathic systemic vasculitis, which will arise in the following conditions:
  • Presence of visible vascular lesions such as purpura, necrotic fingertips etc. 
  • Presence of more or less typical symptoms such as necrotizing inflammation in the upper airways (WG), hypereosinophilia with non-allergic asthma (Churg-Strauss syndrome) etc. 
  • Rapidly progressive glomerulonephritis
  • Presence of symptoms and signs of inflammation such as fever, raised ESR and C-reactive protein level, etc., without identifiable cause or localization

Antibody isotype

IgG

Detection methods

ELISA (with coated PR3) or indirect immunofluorescence (IIF). 90% of cANCA positive sera are also positive in PR3 ELISA and vice versa.

References

  • Gross WL, Csernok E, Szymkowiak CH (1996) Antineutrophil cytoplasmic autoantibodies with specificity for proteinase 3. In: Peter JB, Shoenfeld Y (eds.) Autoantibodies, pp 61-67, Elsevier, Amsterdam 
  • Harris A, Chang G, Vadas M, Gillis D (1999) ELISA is the superior method for detecting antineutrophil cytoplasmic antibodies in the diagnosis of systemic necrotizing vasculitis. J Clin Pathol 52, 670-676 
  • Boomsma MM, Stegeman CA, ven der Leij MJ (2000) Prediction of relapses in Wegener's granulomatosis by measurement of antineutrophil cytoplasmic antibody levels. Arthritis Rheum 43, 2025-2033 

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MPO Antibodies

Products Article No. No. of tests
EliA MPO S (sensitive)  NEW! 14-5537-01 4x12 tests
EliA MPO 14-5513-01 4x12 tests
Varelisa MPO ANCA 176 96 96 tests

Promotion Material

Performance Folders
EliA PR3 S, MPO S (pdf)
EliA PR3, MPO, GBM (pdf)
Varelisa ANCA (pdf)

Antigens

Antineutrophil cytoplasmic antibodies (ANCA) can be subdivided in cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA). The main antigen for the pANCA reactivity is the enzyme myeloperoxidase (MPO). MPO is present in and is a marker enzyme of the azurophilic granules of neutrophils. It catalyzes the production of hypochloric acid, which is effective in killing phagocytized bacteria and viruses.

MPO makes up almost 5% of the total protin of a neutrophilic granulocyte. It is a covalently linked dimer with a molecular weight of about 140 kDa.

MPO in Phadia assays is purified from human neutrophils.

Antibody specificity and prevalence

  • Idiopathic necrotizing and crescentic glomerulonephritis without immune deposits (= pauci-immune) (in about 65%) 
  • Mircroscopic Polyangiitis (45%) 
  • Churg-Strauß Syndrome (about 60%) 
  • Wegener's Granulomatosis, WG (10%) 
  • Polyarteritis Nodosa (about 15%) 
  • Goodpasture Syndrome (about 30-40%) 
  • SLE (about 8%), but more common in drug induced lupus

More information about the diseases

In general, anti-MPO and anti-PR3 do not occur in the same patient concurrently. The detection of p-ANCA with clear MPO activity is 99% specific for necrotizing small vessel vasculitis. In contrast, p-ANCA with negative or low positive MPO reactivity are not associated with vasculitis. A.Wiik, Denmark, suggested that the latter be renamed neutrophil-specific autoantibodies rather than ANCA in order to avoid misinterpretation of results (Carette S., 2004, J Rheumatol 31:792-4).

Disease activity

The relative risk for relapse is increasing with ANCA positivity.

Risk factor for relapse in case of Relative risk
ANCA positive 10%
ANCA increasing 19%
Stop of treatment 2.4%

Table: ANCA persistence or rise should influence therapeutic decision. (Data from a presentation of Jayne J in Geneva 2002)

ANCA titers are higher during active diseases than at remission.

When is the measurement recommended?

  • Suspicion of idiopathic systemic vasculitis, which will arise in the following conditions:
  • Presence of visible vascular lesions such as purpura, necrotic fingertips etc. 
  • Presence of more or less typical symptoms such as necrotizing inflammation in the upper airways (WG), hypereosinophilia with non-allergic asthma (Churg-Strauss syndrome) etc. 
  • Rapidly progressive glomerulonephritis 
  • Presence of symptoms and signs of inflammation such as fever, raised ESR and C-reactive protein level, etc., without identifiable cause or localization

Antibody isotypes

IgG

References

  • Kallenberg CGM (1996) Antineutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase. In: Peter JB, Shoenfeld Y (eds.) Autoantibodies, pp 53-60, Elsevier, Amsterdam 
  • Harris A, Chang G, Vadas M, Gillis D (1999) ELISA is the superior method for detecting antineutrophil cytoplasmic antibodies in the diagnosis of systemic necrotizing vasculitis. J Clin Pathol 52, 670-676 
  • Savage COS, Harper L, Cockwell P, Adu D, Howie AJ (2000) ABC of arterial and vascular disease - Vasculitis. Br Med J 320, 1326-1328

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GBM Antibodies

Products Article No. No. of tests
Varelisa GBM Antibodies 133 96 96 tests
EliA GBM 14-5514-01 2 x 12 tests

Promotion Material

Performance Folder
EliA PR3, MPO, GBM (pdf)

Antigens

The main function of the glomerular basement membrane (GBM) of the kidney is ultrafiltration of blood. Type IV collagen is a typical component of the GBM, has self-aggregating properties and forms a matrix in which the other basement membrane molecules are integrated. Type IV collagen forms trimers that are composed of three subunits of alpha chains. Since the antibodies are directed to epitopes of the so-called "non collagenous domain" (NCI-domain) that are hidden inside the protein in its native structure, there is a need to use denatured antigen for the detection of GBM antibodies.

The Varelisa GBM Antibodies and EliA GBM are the first assays using human recombinant NCI domain of collagen IV alpha 3-chain.

Antibody specificity and prevalence

  • Rapidly progressing Glomerulonephritis (with or whithout lung hemorrhage) (15%) 
  • Goodpasture's Syndrome (one of three specific criteria) 
  • ANCA associated Vasculitides

Goodpasture's syndrome

In Goodpasture's syndrome it is important to initiate therapy before renal damage has advanced too far. Early recognition is therefore mandatory and cen be confirmed with the use of sensitive assays.

Disease activity

Relatively high antibody titers may persist in patients in clear clinical remission and decline only slowly over a year or so. In general, renal transplantation should be postponed until antibody titration is negative to avoid a recurrence of the disease in the transplant recipient. 

When is the measurement recommended?

  • Suspicion of Goodpasture's Syndrome 
  • Patients with Glomerulonephritis 
  • Positive ANCA results 
  • Before kidney transplantation: Indication of a high risk to go into acute renal failure (poor prognosis)

Antibody isotypes

IgG

References

  • Hellmark T, Segelmark M, Bygren P, Wieslander J (1996) Glomerular basement membrane autoantibodies. In: Peter JB, Shoenfeld Y (eds.) Autoantibodies, pp 291-298, Elsevier, Amsterdam 
  • Kluth DC, Rees AJ (1999) Anti-glomerular basement membrane disease. J Am Soc Nephrol 10, 2446-2453 
  • Gibson IW, More IAR (1998) Glomerular pathology: Recent advances. J Pathol 184, 123-129

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