Autoantibodies

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
  • 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
  • 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-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