ANA
(significant only if >1:160 titer)
- Scleroderma (95% of cases)
- SLE (X% of cases)
- xxx
c-ANCA
- Wegener’s (80-90% of cases): high titers correlate well with active granulomatous vasculitis
p-ANCA
(titers are much less specific than c-ANCA titers)
- Microscopic polyangiitis (70% of cases)
- Churg-Strauss (50% of cases)
- UC
- xxx
Anti-Ribonucleoprotein
- MCTD
Anti-dsDNA
- xxx
Anti-Ro
- SLE: positive titer in pregnant patient with SLE indicates high risk of neonatal heart block
Anti-Scl70 (Anti-Topoisomerase)
- Scleroderma (20% of cases): increases risk of cutaneous disease and increases risk of ILD (16.7-fold)
Anti-Centromere
- Scleroderma: high specificity
- Associated with limited cutaneous disease and CREST
Myositis-Specific Autoantibodies
-
Anti-aminoacyl-tRNA synthetases (anti-jo-1/antiPL-7): variable course, significant mortality
- Polymyositis: clinical features include acute onset with ILD, arthritis, hyperkeratotic rash on hands (“mechanic’s hands”)
-
Anti-Signal Recognition Peptide: poor prognosis (5-year mortality is 75%)
- Polymyositis: clinical features include hyperacute onset with cardiac involvement/onset in fall/more prevalent in black females
-
Anti-MI2 (components of histone acetylase complexes): good prognosis
- Polymyositis: clinical features include dermatomyositis, shawl sign of rash, cuticular overgrowth
Anti-Saccharomyces Cerevisiae (ASCA)
- Crohn’s
Anti-Mitochondrial
- PBC (usually >1:40)
Anti-Smooth Muscle
- Autoimmune hepatitis
Anti-Thyroglobulin
- xxx
Anti-GBM
- Goodpasture’s
Rheumatoid Factor
- RA
- Advanced age
- Chronic liver disease
- Chronic infections
- Pulmonary fibrosis
—
Scleroderma (see Scleroderma)
- ANA
- Positive in 90-100% of cases
- Anti-Centromere: targets centromere proteins (CENP A-F)
- Positive in 20-40% of Scleroderma cases
- Positive in 57% of cases with limited cutaneous disease
- Associated with CREST syndrome
- Positive in 70-80% of cutaneous Scleroderma cases with associated pulmonary hypertension
- Anti-Centromere appears to be protective against the development of interstitial lung disease
- It is rare to have both Scl-70 and anti-centromere antibodies
- High specificity for scleroderma
- Scl-70: targets DNA topoisomerase I
- Positive in 28-70% of Scleroderma cases (however, there is wide racial variation)
- Positive in 40% of diffuse cutaneous Scleroderma cases with associated with interstitial lung disease
- Increases risk of scleroderma-associated ILD by 16.7x
- PM-Scl: present in Scleroderma-myositis overlap syndromes
- Antinucleolar: targets RNA polymerase I
- Positive in 8-20% of Scleroderma cases
- Presence predicts poorest 10-year survival and renal crises
- High specificity for scleroderma
- Ku: targets DNA binding proteins
- Antinucleolar: targets RNA polymerase I
- U1-RNP: targets small nuclear proteins
- Positive in 8% of cases
- Positive in 14% of limited cutaneous Scleroderma cases
- Positive in 3% of diffuse cutaneous Scleroderma cases
- Positivity is correlated with presence of interstitial lung disease and joint involvement
- Positive in 8% of cases
- Anti-U3 Nucleolar RNP
- Highly specific for scleroderma
- More common in African-Americans
- Associated with skeletal muscle disease and pulmonary hypertension
- RF: present at low titer in 25% of cases
Rheumatoid Arthritis (see Rheumatoid Arthritis)
- Rheumatoid Factor: targets IgG
- Seropositivity is more frequent with pulmonary rheumatoid nodules
- ANA
- Anti-Histone: targets histone proteins
- Positive in 5% of rheumatoid vasculitis cases
SLE (see SLE)
ANA
- ANA Assay: typically uses HEP-2 cells -> detects multiple cytoplasmic and nuclear antigens (DNA, histone proteins, and chromatin)
- Sensitivity for SLE: 90-95%
- Specificity for SLE: low
- Usually 1:160 is the cutoff titer for a significant positive ANA
- ANA may be positive (usually at low titer) with advancing age, other autoimmune diseaeses, viral infection, and chronic inflammation
- Anti-DNA (70%): associated with disease activity and nephritis
- Anti-dsDNA: targets double-stranded DNA
- Sensitivity for SLE: 50-75%
- Specificity for SLE: high
- In conjunction with low complement levels, anti-dsDNA is strongly associated with disease activity
- Anti-ssDNA (targets single-stranded DNA): not SLE-specific
- Anti-dsDNA: targets double-stranded DNA
- Anti-Sm: targets protein complexed to small nuclear RNA
- Sensitivity for SLE: 30%
- Specificity for SLE: high (most specific anitbody for SLE)
- Anti-Histone: targets histone proteins
- Sensitivity for Idiopathic SLE: 70%
- Sensitivity for Drug-Induced SLE: 95%
- Anti-Ro: targets RNA transcription factors
- Sensitivity for SLE: 30%
- Associated with renal disease
- Positive in 80% of Acute Lupus Pneumonitis cases (probably forms immune complexes, which are deposited in the lungs)
- Anti-La: targets RNA transcription factors
- Sensitivity for SLE: 10%
- Always associated with anti-Ro
- Associated with renal disease
- Anti-RNP: targets ribonucleoprotein complexed to U1RNA
- Sensitivity: 40%
- If present in SLE without anti-DNA< risk of renal disease is low
Anti-Phospholipid Antibodies
- Anti-Cardiolipin
- Positive in 50% of SLE cases
- Associated with increased risk of venous and arterial thrombosis, thromobcytopenia, valvular heart disease, and spontaneous abortion
- Associated with prolonged PTT and false-positive VDRL
- Lupus Anticoagulant
- Positive in 20-30% of SLE cases
- Assay: Russell Viper Venom or RBNP
- Associated with increased risk of thrombosis
Other Autoantibodies
- Anti-Neuronal: targets neuronal or lymphocyte surface antigens
- Sensitivity for SLE: 60%
- High CSF IgG titers are associated with diffuse CNS disease
- Anti-Erythrocte: targets erythrocyte surface antigens
- Sensitivity for SLE: 60%
- Small perecentage of these patients develop hemolysis
- Anti-Platelet: targets platelet surface antigens
- Sensitivity for SLE: unknown
- Anti-Lymphocyte: targets lymphocyte surface antigens
- Sensitivity for SLE: 70%
- Probably associated with leukopenia and abnormal T-cell function
- Rheumatoid Factor (RF)
- Sensitivity for SLE: 20%
- ANCA: negative
- Anti-GBM: negative
Mixed Connective Tissue Disease (see Mixed Connective Tissue Disease)
- U1-RNP: targets small nuclear proteins
- Usually positive at >1:1600 (at >1:10,000 titer, this is almost diagnostic of MCTD), but not in all cases
- Positive in myositis-overlap syndromes
- U2-RNP
- Positive in myositis-overlap syndromes
Polydermatomyositis (see Polydermatomyositis)
- Jo-1: targets histidyl tNRA synthetase
- Positive in 20-30% of cases with inflammatory myopathy
- Positive in 50-100% of cases with inflammatory myopathy and interstitial lung disease
- PL-7: targets threonyl tNRA synthetase
- Positive in <3% of cases with antisynthetase syndrome
- PL-12: targets alanyl tNRA synthetase
- Positive in <3% of cases with antisynthetase syndrome
- EJ: targets glycyl tNRA synthetase
- Positive in <2% of cases with antisynthetase syndrome
- OJ: targets isoleucyl tNRA synthetase
- Positive in <2% of cases with antisynthetase syndrome
- Mi-2: targets nuclear proteins
- Positive in <8% of dermatomyositis cases
- Associated with acute onset of classic dermatomyositis
- Ku: targets nuclear proteins
- Associated with myositis-connective tissue disease overlap syndromes
- Anti-Cytoplasmic Ribonucleoprotein (positive in 30% of cases of inflammatory myositis): considered a myositis-specific Ab
- ANCA: negative
Antiphospholipid Antibody Syndrome (see Anti-Phospholipid Antibody Syndrome)
- Anticardiolipin: targets membrane phospholipid
- Lupus Anticoagulant: targets membrane phospholipid
Relapsing Polychondritis (see Relapsing Polychondritis)
- Anti-Cartilage: targets cartilage
- Anti-Collagen: targets collagen
Sjogren’s Syndrome (see Sjogren’s Syndrome)
- Ro (SS-A): targets RNA transcription factors
- Positive in 40-50% of primary Sjogren’s syndrome
- La (SS-B): targets RNA transcription factors
- Positive in 50% of cases
Wegener’s Granulomatosis (see Wegener’s Granulomatosis)
- c-ANCA: cytoplasmic staining, targets mainly proteinase 3 (PR3)
- Positive (>1:20) in >90-95% of untreated active systemic Wegener’s Granulomatosis cases
- Positive in only 60-65% of limited Wegener’s Granulomatosis cases
Churg-Strauss Syndrome (see Churg-Strauss Syndrome)
- p-ANCA: perinuclear pattern, targets mainly myeloperoxidase
- Positive in about 40-70% of patients
Microsopic Polyangiitis (see Microscopic Polyangiitis)
- p-ANCA: perinuclear pattern, targets mainly myeloperoxidase
- Positive in 50-75%
Goodpasture’s Syndrome (see Goodpasture’s Syndrome)
- Anti-GBM
- Sensitivity: >90%
- Specificity: >95%
- p-ANCA: perinuclear pattern, targets mainly myeloperoxidase
- May be positive in some cases with more systemic vasculitis (with rash, myalgias, fever) and a greater tendency to relapse
Polyarteritis Nodosa (see Polyarteritis Nodosa)
- p-ANCA: perinuclear pattern, targets mainly myeloperoxidase
- May be positive
References
- Distribution and antigen specificity of anti-U1RNP antibodies in patients with systemic sclerosis. Clin Exp Immunol. 1999 August; 117(2): 383–387