Vasculitis

Clinical information

According to the consensus introduced at the Chapel-Hill-Consensus conference and the generally renowned classification system, granulomatosis with polyangiitis (GPA, formerly: Wegener’s granulomatosis, WG), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA, formerly: Churg-Strauss syndrome (CSS)) are classed as the group of ANCA-associated vasculitides (AAV). ANCA (antineutrophil cytoplasm antibodies) are autoantibodies directed against antigens found in cytoplasmic granules of neutrophils and monocytes. They are important serological markers for the diagnosis of AAV.

Moreover, an association with ANCA has been described for some of the immune complex vasculitides. Patients with anti-GBM glomerulonephritides (serological marker: antibodies against the glomerular basement membrane; anti-GBM) are often ANCA positive (>35%). A positive result can indicate rapid-progressive glomerulonephritis or GPA. In patients with AAV with renal involvement, the parallel analysis of ANCA and anti-GBM antibodies is thus recommended.

Diagnostics

AAV diagnostics are primarily based on IIFT. Standard for IIFT is a BIOCHIP mosaic of ethanol (EOH)- and formaldehyde (HCHO)-fixed human granulocytes. Further EUROIMMUN-exclusive BIOCHIPs, e.g. HEp-2 cells with sedimented granulocytes, further increase the diagnostic certainty. The EUROPLUS technique allows the combination of conventional cell culture substrates with defined single antigens (PR3, MPO, GBM) on one test field. This considerably simplifies the interpretation of the immunofluorescence patterns.

IIFT allows the differentiation of two ANCA types: the cytoplasmic type (cANCA), which mostly is associated with GPA and is almost always directed against proteinase 3 (PR3), and the perinuclear type (pANCA), which indicates a spectrum of various diseases. The main target antigen of pANCA in MPA and EGP is myeloperoxidase (MPO), but antibodies against granulocyte elastase, lactoferrin, lysozyme, cathepsin G, beta-glucoronidase, azurocidin, h-lamp-2 and alpha-enolase are also found in connection with pANCA.

Positive IIFT results should always be confirmed with a monospecific anti-PR3 and anti-MPO test (e.g. ChLIA and ELISA) (International Consensus Statement, Savige et al., Am J Clin Pathol, 1999 & 2003). Since not all cANCA and pANCA are positive in the ELISA, the highest sensitivity and specificity for ANCA detection can only be achieved with parallel performance of IIFT and ChLIA/ ELISA.

The sCD163 ELISA is therefore especially suited for targeted monitoring of patients with diagnosed AAV with renal involvement. As opposed to systemic inflammation markers, the sCD163 level is a specific indicator for renal inflammation and reacts promptly under treatment or when the inflammatory activity deviates.

pANCA are also of great relevance in the differentiation of chronic inflammatory bowel diseases (67% ulcerative colitis, 7% Crohn’s disease). DNA-bound lactoferrin has been identified as the main target antigen (Teegen et al., Ann N Y Acad Sci, 2009).

Selected Products

Method
Parameter
Substrate
Species
IIFT
antibodies against granulocyte cytoplasm,
cytoplasmic pattern (cANCA control, PR3 ab control)
IIFT
cytoplasm of granulocytes (cANCA,
pANCA), nuclei of granulocytes (GS-ANA)
granulocytes,
ethanol-fixed
human
IIFT
cytoplasm of granulocytes (cANCA,
pANCA), nuclei of granulocytes (GS-ANA)
EUROPattern
granulocytes,
ethanol-fixed
human
IIFT
antibodies against granulocyte cytoplasm,
aliquots from positive control for ANCA diagnostics
(10 different fluorescence patterns)
ELISA
ANCA Profile (proteinase 3, MPO, elastase,
cathepsin G, BPI, lactoferrin separately)
antigen-coated
microplate wells
EUROLINE
positive control serum: IgG, human, 100x concentrated
for DL 1200-X G
EUROLINE
myeloperoxidase (MPO)
proteinase 3 (PR3)
EUROLINE
IIFT
antibodies against granulocyte cytoplasm, cytoplasmic pattern
(cANCA control, PR3 ab control), control serum with indication of titer
EUROLINE
myeloperoxidase (MPO)
proteinase 3 (PR3)
glomerular basement membrane (GBM)
EUROLINE
IIFT
granulocytes
(cANCA, pANCA)
granulocytes,
formaldehyde-fixed
human
IIFT
granulocytes
(cANCA, pANCA)
EUROPattern
granulocytes,
formaldehyde-fixed
human
ChLIA
Control set
Proteinase 3 (PR3)
ChLIA
proteinase 3 (PR3)
Antigen-coated magnetic particles
IIFT
Granulocyte Mosaic 13
cANCA, pANCA, GS-ANA
cell nuclei (ANA), cANCA, pANCA
cANCA, pANCA
3 BIOCHIPs per field:
granulocytes (EOH)
HEp-2+granulocytes (EOH)
granulocytes (HCHO)

human
human
human
IIFT
Granulocyte Mosaic 13 EUROPattern
cANCA, pANCA, GS-ANA, EUROPattern
cell nuclei (ANA), cANCA, pANCA
cANCA, pANCA, EUROPattern
3 BIOCHIPs per field:
granulocytes (EOH)
HEp-2+granulocytes (EOH)
granulocytes (HCHO)

human
human
human
IIFT
Granulocyte Mosaic 15
cANCA, pANCA, GS-ANA
cell nuclei (ANA), cANCA, pANCA
2 BIOCHIPs per field:
granulocytes (EOH)
HEp-2+granulocytes (EOH)

human
human
IIFT
Granulocyte Mosaic 15 EUROPattern
cANCA, pANCA, GS-ANA, EUROPattern
cell nuclei (ANA), cANCA, pANCA
2 BIOCHIPs per field:
granulocytes (EOH)
HEp-2+granulocytes (EOH)

human
human
IIFT
Granulocyte Mosaic 17
cANCA, pANCA, GS-ANA
cANCA, pANCA
cANCA, pANCA
cell nuclei (ANA), cANCA, pANCA
4 BIOCHIPs per field:
granulocytes (EOH)
granulocytes (HCHO)
granulocytes (MOH)
HEp-2+granulocytes (EOH)

human
human
human
human
ELISA
cANCA:
proteinase 3
(PR3-hn-hr)
antigen-coated
microplate wells
IIFT
Granulocyte Mosaic 2
cANCA, pANCA, GS-ANA
cANCA, pANCA
2 BIOCHIPs per field:
granulocytes (EOH)
granulocytes (HCHO)

human
human
IIFT
Granulocyte Mosaic 2 EUROPattern
cANCA, pANCA, GS-ANA, EUROPattern
cANCA, pANCA, EUROPattern
2 BIOCHIPs per field:
granulocytes (EOH)
granulocytes (HCHO)

human
human
IIFT
EUROPLUS Granulocyte Mosaic 20
cANCA, pANCA, GS-ANA
pANCA: myeloperoxidase (MPO)
cANCA: proteinase 3 (PR3)
3 BIOCHIPs per field:
granulocytes (EOH)
MPO BIOCHIPs
PR3 BIOCHIPs

human
IIFT
EUROPLUS Granulocyte Mosaic 22
cANCA, pANCA, GS-ANA
cANCA, pANCA
pANCA: myeloperoxidase (MPO)
cANCA: proteinase 3 (PR3)
4 BIOCHIPs per field:
granulocytes (EOH)
granulocytes (HCHO)
MPO BIOCHIPs
PR3 BIOCHIPs

human
human
IIFT
EUROPLUS Granulocyte Mosaic 22
EUROPattern
cANCA, pANCA, GS-ANA, EUROPattern
cANCA, pANCA, EUROPattern
pANCA: myeloperoxidase (MPO), EUROPattern
cANCA: proteinase 3 (PR3), EUROPattern
4 BIOCHIPs per field:

granulocytes (EOH)
granulocytes (HCHO)
MPO BIOCHIPs
PR3 BIOCHIPs


human
human
IIFT
EUROPLUS Granulocyte Mosaic 25
cANCA, pANCA, GS-ANA
cell nuclei (ANA), cANCA, pANCA
cANCA, pANCA
glomerular basement membrane (GBM)
pANCA: myeloperoxidase (MPO)
cANCA: proteinase 3 (PR3)
6 BIOCHIPs per field:
granulocytes (EOH)
HEp-2+granulocytes (EOH)
granulocytes (HCHO)
GBM BIOCHIPs
MPO BIOCHIPs
PR3 BIOCHIPs

human
human
human
IIFT
EUROPLUS Granulocyte Mosaic 25
EUROPattern
cANCA, pANCA, GS-ANA, EUROPattern
cell nuclei (ANA), cANCA, pANCA
cANCA, pANCA, EUROPattern
glom. basement membrane (GBM), EUROPattern
pANCA: myeloperoxidase (MPO), EUROPattern
cANCA: proteinase 3 (PR3), EUROPattern
6 BIOCHIPs per field:

granulocytes (EOH)
HEp-2+granulocytes (EOH)
granulocytes (HCHO)
GBM BIOCHIPs
MPO BIOCHIPs
PR3 BIOCHIPs


human
human
human
IIFT
EUROPLUS Granulocyte Mosaic 32
cANCA, pANCA, GS-ANA
cANCA, pANCA
cell nuclei (ANA), cANCA, pANCA
pANCA: myeloperoxidase (MPO)
cANCA: proteinase 3 (PR3)
5 BIOCHIPs per field:
granulocytes (EOH)
granulocytes (HCHO)
HEp-2+granulocytes (EOH)
MPO BIOCHIPs
PR3 BIOCHIPs

human
human
human
IIFT
EUROPLUS Granulocyte Mosaic 32
EUROPattern
cANCA, pANCA, GS-ANA, EUROPattern
cANCA, pANCA, EUROPattern
cell nuclei (ANA), cANCA, pANCA
pANCA: myeloperoxidase (MPO), EUROPattern
cANCA: proteinase 3 (PR3), EUROPattern
5 BIOCHIPs per field:

granulocytes (EOH)
granulocytes (HCHO)
HEp-2+granulocytes (EOH)
MPO BIOCHIPs
PR3 BIOCHIPs


human
human
human
IIFT
Granulocyte Mosaic 4
cANCA, pANCA, GS-ANA
cANCA, pANCA
cell nuclei (ANA)
3 BIOCHIPs per field:
granulocytes (EOH)
granulocytes (HCHO)
HEp-2 cells

human
human
human
IIFT
Granulocyte Mosaic 4 EUROPattern
cANCA, pANCA, GS-ANA, EUROPattern
cANCA, pANCA, EUROPattern
cell nuclei (ANA)
3 BIOCHIPs per field:
granulocytes (EOH)
granulocytes (HCHO)
HEp-2 cells

human
human
human
IIFT
Granulocyte Mosaic 40
cANCA, pANCA, GS-ANA
cell nuclei (ANA), cANCA, pANCA
cANCA, pANCA
DNA-bound lactoferrin (pANCA)
ANCA negative
5 BIOCHIPs per field:
granulocytes (EOH)
HEp-2+granulocytes (EOH)
granulocytes (HCHO)
LFS granulocytes
HSS granulocytes

human
human
human
human
human
IIFT
cytoplasm of granulocytes (cANCA,
pANCA), nuclei of granulocytes (GS-ANA)
granulocytes,
methanol-fixed
human
IIFT
antibodies against granulocyte cytoplasm, perinuclear pattern
(pANCA control, MPO ab control)
ELISA
pANCA:
myeloperoxidase (MPO)
antigen-coated
microplate wells
IIFT
antibodies against granulocyte cytoplasm, perinuclear pattern
(pANCA control, MPO ab control)
control serum with indication of titer
IIFT
antibodies against DNA-bound lactoferrin (pANCA)
(LFS ab control)
IIFT
DNA-bound lactoferrin (pANCA)
ANCA negative
LFS granulocytes
HSS granulocytes
(2 BIOCHIPs per field)
human
IIFT
antibodies against granulocyte cytoplasm,
perinuclear pattern (xANCA control)
ELISA
sCD163
determination in urine
antibody-coated
microplate wells
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