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Systemic Diseases
General screening of autoantibodies allows a quick and
reliable identification of many autoantigens coexistent in
several autoimmune diseases, without compromise of its
organ dependence. Furthermore, many of the connective
tissue autoimmune diseases have been associated to
specific autoantigens that act as markers.
The most accepted screening method is a two-step
approach, where after an initial screening to detect
potential positives, a more refined search is made to
identify the antigen or antigens triggering the immune
response. In this two-step approach, the most common
methods are Immunofluorescence Assay, either on tissue
or cultured cells, and ELISA methods.
ANA
Sensitivity of antinuclear antibodies determination is higher than 95%
for Systemic Lupus Erythematosus (SLE), although specificity is fairly
low.The presence of high levels of specific ANA is also indicative of
other systemic rheumatic diseases such as drug-induced lupus (DIL),
Sjögren’s syndrome, scleroderma and variants, polymyositis and
dermatomyositis, CREST syndrome, mixed connective tissue disease
and rheumatoid arthritis.
• Homogeneous: Indicative of SLE.
• Speckled: Highly related to SLE, mixed connective tissue disease,
Sjögren’s syndrome, polymyositis or scleroderma.
• Centromeric: In patients with systemic sclerosis, especially in a
cutaneous limited form of the disease (80%). Occasionally, in some other
connective diseases.
• Nucleolar: In approximately 50-70% of the patients with overlapping
scleroderma and polymyositis/dermatomyositis syndromes. They are
found in up to 33% of patients with systemic scleroderma, specially
those with renal complications.
ENA
The presence of high levels of specific ENA antibodies is indicative
of systemic rheumatic diseases such as SLE, Sjögren’s syndrome,
scleroderma, polymyositis, mixed connective tissue disease or
rheumatoid arthritis. Some individuals may have high levels of antibodies
to ENA with no evidence of clinical disease. By contrast, patients with
systemic rheumatic diseases may have undetectable levels of such
antibodies. It is recommended that sera, which are positive for ENA, are
tested to determine the specific antibody with single specificity kits.
• SSA(Ro) is indicative of primary Sjögren’s syndrome and SLE. These
antibodies are found in approximately 60-70% of the patients with
Sjögren’s syndrome and 40-50% of the patients with SLE.
• SSB (La) is indicative of primary Sjögren’s syndrome and SLE. These
antibodies are found in approximately 10-40% of the patients with
Sjögren’s syndrome and 6-15% of the patients with SLE.
• Sm is strongly indicative of SLE. These antibodies are found in
approximately 20-30% of the patients with the disease.
• Sm/RNP is indicative of SLE and mixed connective tissue disease.
These antibodies are found in approximately 30-40% of the patients with
SLE and 100% of the patients with Mixed Connective Tissue Disease.
• Scl-70 are directed against DNA-topoisomerase I. They are highly
specific for systemic scleroderma and give a hint for a severe course.
• Jo-1 are directed against histidyl-tRNA synthetase (cytoplasmic protein
involved in protein biosynthesis) and are found in 20-40 % of patients
with polymyositis and dermatomyositis.
• CENP-B (80kDa centromere protein B): Anti-centromere B antibodies
are found in patients with systemic sclerosis (SSc), specially in a
cutaneous limited form of the disease and with the absence of pulmonary
involvement. They are typical for the CREST syndrome (69% of CREST
patients), a subclase of SSc which is a more protracted type of systemic
sclerosis.
RIBOSOME P
Autoantibodies to ribosomal P protein are present in 10-20% of patients
with SLE, but frequencies up to 38% are found in different ethnic groups
and young onset SLE. Association of anti-ribosomal P protein antibodies
with active SLE, kidney disease and liver disease has been demonstrated,
but correlation with neuropsychiatric lupus is not clear.
HISTONES
Antibodies against histones are observed in 20-50% of patients with
spontaneous SLE and in 50-90% of drug induced lupus erythematosus.
These autoantibodies are not specific for SLE since they are found also in
drug induced lupus erythematosus (three times higher incidence than in
SLE) and in rheumatoid arthritis.
Homogeneous pattern
Anti-centromere antibodies
Nucleolar pattern
Speckled pattern
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