Connective tissue diseases

Clinical information

Connective tissue diseases (CTD) are rheumatic diseases and include, for example, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, myositis syndromes and Sharp syndrome.

Autoantibodies against cellular components, commonly called anti-nuclear antibodies (ANA), are important serological markers for CTD. Target antigens include nucleic acids, cell nuclear proteins and ribonuclear proteins as well as components of the cytoplasm. The frequency (prevalence) of ANA in systemic rheumatic diseases varies between 20 % and 100 %. The different target antigens are associated with different rheumatic diseases. Multi-tier ANA diagnostics is therefore indispensable for differentiation of the specific antibodies in order to distinguish individual rheumatic diseases as well as to differentiate them 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. In the microscopic evaluation it is possible to establish precisely how an indicator dye (generally fluorescein) is distributed in the cells. Depending on the location of the individual autoantigens, a typical fluorescence pattern for every type of autoantibody bound will appear.

The revised international consensus on a standardised nomenclature of HEp-2 cell patterns in indirect immunofluorescence (ICAP, www.anapatterns.org) defines 15 nuclear, 9 cytoplasmic and 5 mitotic patterns which are relevant for the diagnostics of various autoimmune diseases.

The EUROIMMUN BIOCHIP technology allows to combine HEp-2 cell substrates with organ sections (liver), which supports the identification and differentiation of certain patterns. Users can choose between HEp-2 cells and HEp-20-10 cells. The latter contain a far greater number of cells in mitosis, which facilitates pattern interpretation.

For confirmation of IIFT results ICAP recommends to subsequently perform specific antibody tests (e.g. ELISA, line blot, ChLIA). However, the exclusive use of these monospecific test methods is insufficient for the determination of ANA, as not all relevant antigens are available yet in purified form. Thus, the corresponding ANA can only be detected by IIFT. 

Files

Strategy for the Determination of ANA and Cytoplasm Components

The optimal choice for ANA diagnostics

ELISA test systems for the determination of antibodies against nuclear and cytoplasmic antigens

EUROLINE Nuclear and Cytoplasmic Antigen Profiles

EUROLINE myositis profiles

EUROLINE systemic sclerosis profiles

Chemiluminescent immunoassays for rheumatic disease diagnostics