Connective tissue diseases

Clinical information

Connective tissue diseases (CTD) are rheumatic diseases. They include, for example, systemic lupus erythematosus (see chapter SLE), progressive systemic sclerosis, Sjögren's syndrome, myositis or Sharp syndrome. Autoantibodies whose target antigens are located in the nucleus (so-called anti-nuclear antibodies, ANA) are important serological markers for CTD. Target antigens include, for example, nucleic acids, cell nuclear proteins and ribonuclear proteins. The frequency (prevalence) of anti-nuclear antibodies in inflammatory rheumatic diseases lies between 20 and 100 %. Therefore, differential ANA diagnostics is indispensable for the diagnosis of individual rheumatic diseases and their differentiation from other autoimmune diseases.

Diagnostics

The gold standard for the determination of ANA is the indirect immunofluorescence test (IIFT) with human epithelial cells (HEp-2), which is known for its high sensitivity and specificity. Positive and negative samples produce a large signal difference. In the microscopic evaluation it is possible to establish precisely how an indicator dye (generally fluorescein) is distributed in the tissue or the cells. A typical fluorescence pattern is produced for every bound autoantibody, depending on the location of the individual autoantigens.

The first international consensus on standardised nomenclature of HEp-2 cell patterns in indirect immunofluorescence (ICAP, www.anapatterns.org) defined fifteen nuclear patterns and nine cytoplasmic patterns which are relevant for the diagnosis of various autoimmune diseases.

Furthermore, the consensus recommends that autoantibodies detected in indirect immunofluorescence be confirmed by additional specific tests (e.g. ELISA, line blot). The exclusive use of these monospecific test methods is inadequate for the determination of autoantibodies against cell nuclei, as not all relevant antigens are available in a purified form as yet. Thus, the corresponding ANA can only be detected by IIFT.

Selected Products

MethodParameterSubstrateSpecies 
IIFTcell nuclei
(ANA global test)
HEp-2 cells
liver
(2 BIOCHIPs per field)
human
monkey
Details
IIFTcell nuclei (ANA) EUROPattern
cell nuclei (ANA)
HEp-2 cells
liver
(2 BIOCHIPs per field)
human
monkey
EUROPLUS ANA Mosaic 10
cell nuclei (ANA)
SS-A + SS-B
2 BIOCHIPs per field:
HEp-2 cells
SS-A+SS-B BIOCHIPs
human
cell nuclei (ANA)
mitochondria (AMA)
HEp-2 cells
kidney
(2 BIOCHIPs per field)
human
rat
ANA Mosaic 2 EUROPattern
cell nuclei (ANA), EUROPattern
mitochondria (AMA)
2 BIOCHIPs per field:
HEp-2 cells
kidney
human
rat
cell nuclei
(ANA global test)
HEp-20-10 cells
liver
(2 BIOCHIPs per field)
human
monkey
cell nuclei (ANA) EUROPattern
cell nuclei (ANA)
HEp-20-10 cells
liver
(2 BIOCHIPs per field)
human
monkey
EUROPLUS ANA Mosaic 10A
cell nuclei (ANA)
SS-A + SS-B
2 BIOCHIPs per field:
HEp-20-10 cells
SS-A+SS-B BIOCHIPs
human
cell nuclei (ANA)
mitochondria (AMA)
HEp-20-10 cells
kidney
(2 BIOCHIPs per field)
human
rat
cell nuclei (ANA) EUROPattern
mitochondria (AMA)
HEp-20-10 cells
kidney
(2 BIOCHIPs per field)
human
rat
EUROPLUS ANA Mosaic 20A
cell nuclei (ANA)
cell nuclei (ANA)
SS-A + SS-B
ribosomal P-proteins + Jo-1
4 BIOCHIPs per field:
HEp-20-10 cells
liver
SS-A+SS-B BIOCHIPs
rib. P-prot.+Jo-1 BIOCHIPs
human
monkey
EUROPLUS ANA Mosaic 22A
cell nuclei (ANA)
cell nuclei (ANA)
nRNP/Sm + Sm + SS-A
SS-B + Scl-70 + Jo-1
4 BIOCHIPs per field:
HEp-20-10 cells
liver
nRNP/Sm+Sm+SS-A BIOCHIPs
SS-B+Scl-70+Jo-1 BIOCHIPs
human
monkey
cell nuclei (ANA)
cell nuclei (ANA)
HEp-20-10 cells
liver
(2 BIOCHIPs per field)
human
rat
cell nuclei (ANA)HEp-2 cellshuman
cell nuclei (ANA)
EUROPattern
HEp-2 cellshuman
cell nuclei (ANA)HEp-20-10 cellshuman
cell nuclei (ANA)
EUROPattern
HEp-20-10 cellshuman
EUROLINEpositive control serum: IgG, human, 100x concentrated
for DL 1530-X G
EUROLINEMyositis Profile
(Mi-2, Ku, PM-Scl, Jo-1, PL-7,
PL-12, Ro-52 separately)
EUROLINE
EUROLINEMyositis Profile 3
(Mi-2, Ku, PM-Scl100, PM-Scl75, Jo-1, SRP,
PL-7, PL-12, EJ, OJ, Ro-52 separately)
EUROLINE
Autoimmune Inflammatory Myopathies 16 Ag
(Mi-2 alpha, Mi-2 beta, TIF1g, MDA5, NXP2, SAE1, Ku, PM-Scl100,
PM-Scl75, Jo-1, SRP, PL-7, PL-12, EJ, OJ, Ro-52 separately)
Autoimmune Inflammatory Myopathies 16 Ag et cN-1A
(Mi-2 alpha, Mi-2 beta, TIF1g, MDA5, NXP2, SAE1, Ku,
PM-Scl100, PM-Scl75, Jo-1, SRP, PL-7, PL-12, EJ, OJ,
Ro-52, cN-1A separately)
positive control serum: IgG, human, 100x concentrated
for DL 1532 G
Systemic Sclerosis Profile (Nucleoli)
(Scl-70, CENP A, CENP B, RP11, RP155,
fibrillarin, NOR90, Th/To, PM-Scl100, PM-Scl75,
Ku, PDGFR, Ro-52 separately)
ELISAhistonesantigen-coated
microplate wells
IIFTantibodies against cell nuclei
(ANA control), homogeneous pattern
test performance control
(ANA homogeneous, IgG)
antibodies against cell nuclei,
aliquots from positive control for ANA diagnostics
(20 different fluorescence patterns)
antibodies against cell nuclei (ANA control),
homogeneous pattern, control serum with indication of titer
antibodies against cell nuclei (ANA control),
homogeneous pattern, for EUROPattern
ELISAdouble-stranded DNA
(dsDNA)
antigen-coated
microplate wells
RIAdouble-stranded DNA (dsDNA)
precipitation
labelled antigen
IIFTantibodies against dsDNA
(dsDNA ab control)
ELISAdsDNA-NcXantigen-coated
microplate wells
dsDNAflagellatesCrithidia luciliae
dsDNA
EUROPattern
flagellatesCrithidia luciliae
dsDNA (sensitive)flagellatesCrithidia luciliae
dsDNA (sensitive)
EUROPattern
flagellatesCrithidia luciliae
antibodies against dsDNA (dsDNA ab control)
control serum with indication of titer
ELISAnucleosomesantigen-coated
microplate wells
single-stranded DNA
(ssDNA)
antigen-coated
microplate wells
IIFTantibodies against cell nuclei
(ANA control), nucleolar pattern
ELISAPM-Sclantigen-coated
microplate wells
IIFTantibodies against cell nuclei
(ANA control), granular pattern

EUROLINE
positive control serum: IgG, human, 100x concentrated
for DL 1590-X G
EUROASSAYAnti-ENA ProfilePlus
(nRNP/Sm, Sm, SS-A, SS-B, Scl-70,
Jo-1 separately)
EUROASSAY strip
with antigens
EUROLINEAnti-ENA ProfilePlus 1
(nRNP/Sm, Sm, SS-A, Ro-52, SS-B,
Scl-70, Jo-1 separately)
EUROLINE
ELISAAnti-ENA ProfilePlus 1 (nRNP/Sm,
Sm, SS-A, SS-B, Scl-70, Jo-1 separately)
antigen-coated
microplate wells
ELISAANA screen 11 (antigen mixture: PCNA,
PM-Scl, ribosomal P-proteins, nRNP/Sm,
Sm, SS-A, Ro-52, SS-B, Scl-70, Jo-1,
centromeres)
antigen-coated
microplate wells
Anti-ENA SLE Profile 2 (dsDNA, histones,
nucleosomes, nRNP/Sm, Sm,
SS-A, SS-B, Scl-70 separately)
antigen-coated
microplate wells
ANA screen 9 (antigen mixture: PCNA,
PM-Scl, ribosomal P-proteins, nRNP/Sm,
Sm, SS-A, SS-B, Scl-70, Jo-1)
antigen-coated
microplate wells
EUROASSAYAnti-ENA ProfilePlus with AMA M2
(nRNP/Sm, Sm, SS-A, SS-B, Scl-70,
Jo-1, AMA M2 separately)
EUROASSAY strip
with antigens
ELISAAnti-ENA ProfilePlus 2 (ribosomal
P-proteins, nRNP/Sm, Sm, SS-A, SS-B,
Scl-70, Jo-1, centromeres, separately)
antigen-coated
microplate wells