| Autoimmune diseases are serologically characterized
by the occurrence of autoantibodies or autoantibody profiles of different
specificity. The majority of these autoantibodies are directed against
antigens located in the cells' nuclei, the nuclear plasma and matrix,
but also against nucleolic, cytoplasmatic, mitochondrial or microsomal
antigens.
Rheumatoid diseases are mainly associated with the occurrence
of anti-nuclear antibodies (ANA). Some of these ANA are disease-specific
and therefore can bes used as serological markers in the diagnosis.
They include antibodies against:
- Double-stranded DNA (ds-DNA) and the Sm antigen in Systemic Lupus
Erythematodes (SLE)
- Fibrillarin in scleroderma and Scl-70 (Topoisomerase I) are
associated with diffuse scleroderma
- Centromere (ACA) for CREST syndrome
- Histidyl-tRNA-Synthetase (Jo-1) in polymyositis
- PM-Scl in polymyositis and scleroderma overlap syndromes
ANA with different prevalence are found in several diseases,
including
- anti-Histone in SLE, drug-induced Lupus and nutritive toxic
chronic liver diseases;
- anti-RNP in SLE and mixed connective tissue disease (Sharp
Syndrome) and
- anti-SS-A (Ro) and anti-SS-B (La) associated with
SLE and Sjögren
Syndrome (1,2).
Antimitochondrial antibodies (AMA) against the M2 epitope
typically react with mitochondrial proteins of the a-keto
acid-dehydrogenase
complexes and are characteristic markers for primary biliar
cirrhosis (PBC), which is a chronic cholestatic liver disease. The earliest developed method for the detection of ANA and AMA
has been the Immunofluorescence test (IFT) utilizing cryostatic
tissue sections or cells as substrate.
An important criteria for the selection of the appropriate substrates
is the species specificity of relevant antibodies. For some human
antibodies it has been demonstrated that they only react with tissue
substrates of human or primate origin, whereas other types of autoantibodies
also react on tissue sections from rat, mice, rabbit or guinea
pig. This indicates that the respective antigens are distinguishable
with respect to their phylogenetic development and only those antigens
that remained mostly conserved during evolution can be found in
species of less close relationship.
Utilization of HEp2 cells, a human Larynx Epithelioma cell line
with high specificity for most of the human ANA and ENA antibodies,
circumvents the disadvantage and limitation of substrates of animal
origin that are not suitable for the detection of several autoantibody
specificities. |