Connective tissue diseases

Clinical information

Connective tissue diseases (CTD) are rheumatic diseases. They include, for example, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, myositis syndromes or 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 inflammatory rheumatic diseases lies between 20% and 100%. Differential ANA diagnostics is therefore indispensable for the identification 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. 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.

Furthermore, ICAP recommends that IIFT results be confirmed by additional specific antibody tests (e.g. ELISA, line blot, ChLIA). However, the exclusive use of these monospecific test methods is insufficient for the determination of autoantibodies against cell nuclei, as not all relevant antigens are available yet in purified form. Thus, the corresponding ANAs can only be detected by IIFT.