Antinuclear antibodies (ANA)
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Background
Antinuclear antibodies (ANA) are a family of autoantibodies directed against components of the cell nucleus, including DNA, RNA, and associated proteins. They are a hallmark of autoimmune diseases. They are sometimes referred to as antinuclear factors (ANF).Clinical Significance:
ANA are nonspecific but are strongly associated with autoimmune connective tissue diseases. ANA subtypes matter for specificity (see table below).A positive ANA raises suspicion for connective tissue disease, but is not diagnostic. Subtype testing (anti-dsDNA, anti-Sm, anti-Ro/La, anti-Scl-70, etc.) narrows diagnosis.
| Condition | Frequency of ANA | Typical Notes |
|---|---|---|
| Systemic lupus erythematosus (SLE) | >95% | Often homogeneous or speckled pattern; anti-dsDNA highly specific |
| Sjögren’s syndrome | 60–80% | Anti-SSA/Ro and anti-SSB/La common |
| Systemic sclerosis (Scleroderma) | 60–90% | Often nucleolar or centromere pattern |
| Mixed connective tissue disease (MCTD) | 100% | High titre anti-U1-RNP |
| Rheumatoid arthritis | 30–50% | Usually low titre; not diagnostic |
| Polymyositis / Dermatomyositis | 20–50% | Anti-Jo-1 plus various other ENAs |
Interpretation
ANA can be positive in healthy individuals, especially elderly (up to 20% may have low titres). Titre and pattern are important.
Titre:
- Low titre (1:40 or 1:80) may be nonspecific
- High titre (≥1:160) is more clinically significant
Pattern recognition: The staining pattern can give clues about the specific autoantibody present:
- Homogeneous: often anti-dsDNA or histone
- Speckled: often anti-Sm, anti-RNP, anti-SSA/SSB
- Nucleolar: systemic sclerosis
- Centromere: limited cutaneous systemic sclerosis (CREST)
Clinical uses:
- Screening for autoimmune rheumatic diseases
- Supporting diagnosis in combination with clinical features
- Monitoring disease activity (specific antibodies like anti-dsDNA in SLE)
Key Features:
Type: Autoantibodies (IgG most common)
Target: Nuclear antigens such as:
Type: Autoantibodies (IgG most common)
Target: Nuclear antigens such as:
- DNA (double-stranded, dsDNA)
- Histones
- Extractable nuclear antigens (ENAs) like SSA/Ro, SSB/La, RNP, Sm
- Nucleolar proteins
Main ANA subtypes
| ANA subtype class | Antibodies |
|---|---|
| 1. DNA-associated | Anti-dsDNA → highly specific for SLE, correlates with nephritis Anti-ssDNA → less specific, sometimes in SLE or other CTDs |
| 2. Histone-associated | Anti-histone → classic for drug-induced lupus |
| 3. RNA-binding proteins (Extractable Nuclear Antigens, ENAs) | Anti-Sm → highly specific for SLE (though less common) Anti-RNP (U1-RNP) → mixed connective tissue disease (MCTD), also SLE Anti-SSA (Ro) → Sjögren’s syndrome, SLE (especially subacute cutaneous lupus) Anti-SSB (La) → Sjögren’s syndrome Anti-Scl-70 (topoisomerase I) → diffuse systemic sclerosis Anti-centromere → limited systemic sclerosis (CREST) Anti-PM/Scl → overlap of myositis and scleroderma Anti-Jo-1 (histidyl tRNA synthetase) → polymyositis/dermatomyositis Other myositis-associated ENAs → anti-Mi-2, anti-SRP, anti-TIF1γ, etc. |
| 4. Nucleolar antibodies (often systemic sclerosis) | Anti-fibrillarin (U3-RNP) Anti-Th/To Anti-RNA polymerase I/III |
| 5. Other ANA targets | Anti-PCNA (proliferating cell nuclear antigen) → rare, some SLE cases Anti-Ku → overlap syndromes |