What are ANCA (Antineutrophil Cytoplasmic Antibodies) and dsDNA (double-stranded Deoxyribonucleic acid) antibodies?

ANCA and dsDNA Antibodies: Diagnostic Markers in Autoimmune Diseases

ANCA (Antineutrophil Cytoplasmic Antibodies) and dsDNA (double-stranded DNA) antibodies are important autoantibody markers used in diagnosing specific autoimmune conditions, with ANCA primarily associated with small vessel vasculitides and dsDNA being a key marker for systemic lupus erythematosus. 1, 2

ANCA (Antineutrophil Cytoplasmic Antibodies)

ANCA are autoantibodies directed against cytoplasmic components of neutrophils that play a crucial role in diagnosing certain vasculitic disorders 1.

Types and Patterns of ANCA:

• c-ANCA (cytoplasmic pattern): Primarily targets proteinase 3 (PR3) and is strongly associated with Wegener's granulomatosis (granulomatosis with polyangiitis) with 80-90% sensitivity 1, 3

• p-ANCA (perinuclear pattern): Most commonly targets myeloperoxidase (MPO) and is associated with microscopic polyangiitis, pauci-immune crescentic glomerulonephritis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) 1, 3

• Atypical ANCA (a-ANCA): Less common pattern that can be found in conditions other than systemic vasculitis 3

Clinical Significance of ANCA:

• ANCA testing has high diagnostic value for ANCA-associated vasculitides with 85-95% sensitivity in Wegener's granulomatosis, microscopic polyangiitis, and pauci-immune necrotizing glomerulonephritis 2

• p-ANCA can also be found in autoimmune liver diseases (60-92% in primary sclerosing cholangitis), inflammatory bowel disease (60-87% in ulcerative colitis, 5-25% in Crohn's disease), and other autoimmune conditions 1, 4

• ANCA may be useful in monitoring disease activity, particularly in Wegener's granulomatosis, where changes in c-ANCA levels often precede disease flares 4

dsDNA (double-stranded DNA) Antibodies

Anti-dsDNA antibodies are autoantibodies directed against double-stranded DNA and are a key diagnostic marker for systemic lupus erythematosus (SLE) 1.

Characteristics of anti-dsDNA:

• Anti-dsDNA antibodies are heterogeneous and can target various DNA structures, including single-stranded DNA (ssDNA), left-handed dsDNA (Z dsDNA), right-handed dsDNA (B dsDNA), and other nucleic acid structures 1

• They constitute the most prominent immunological criterion in the EULAR/ACR 2019 classification for SLE diagnosis 1

• Anti-dsDNA antibodies can be detected using various methods including solid-phase assays (SPA) and Crithidia luciliae immunofluorescence test (CLIFT) 1

Clinical Significance of anti-dsDNA:

• High specificity for SLE diagnosis, particularly when detected by CLIFT method 1

• Strong association with lupus nephritis and other SLE manifestations including skin involvement and certain neuropsychiatric disorders 1

• Can be found in healthy individuals and other conditions including bacterial and viral infections, parasitic infections, cancer, and other autoimmune syndromes, though typically at lower titers 1

• Useful for monitoring disease activity in SLE patients, with rising titers often correlating with disease flares 1

Important Clinical Considerations

Testing Methods:

• ANCA detection typically involves indirect immunofluorescence followed by confirmation with enzyme-linked immunosorbent assay (ELISA) for specific antigens (PR3, MPO) 3

• Anti-dsDNA testing should include both solid-phase assays (SPA) and CLIFT for optimal diagnostic accuracy 1

Diagnostic Pitfalls:

• A positive ANCA or anti-dsDNA test alone is insufficient for diagnosis and must be interpreted in the clinical context 5

• Different laboratories may use different methods and cutoffs, affecting result interpretation 5

• False positives can occur in various conditions, including infections and malignancies 1, 6

• When suspecting SLE, a negative anti-dsDNA result does not rule out the disease, as some patients may be seronegative initially 1

Clinical Algorithm for Interpreting Results:

• For suspected SLE with positive ANA:

  • If anti-dsDNA is positive by both SPA and CLIFT: SLE is very likely 1
  • If anti-dsDNA is positive by SPA but negative by CLIFT: Evaluate in clinical context 1
  • If anti-dsDNA is negative: SLE diagnosis cannot be established at that time, consider repeating tests in 6 months if clinical suspicion remains high 1

• For suspected vasculitis with positive ANCA:

  • c-ANCA with PR3 specificity strongly suggests granulomatosis with polyangiitis 6, 3
  • p-ANCA with MPO specificity suggests microscopic polyangiitis or eosinophilic granulomatosis with polyangiitis 6, 3

By understanding these autoantibodies and their clinical significance, clinicians can more accurately diagnose and monitor autoimmune diseases, leading to improved patient outcomes.