Autoantibodies in rheumatic diseases

Last updated: June 19, 2023

Summary

Antibody diagnostics play a vital role in the differential diagnosis of rheumatic diseases. Many of these autoantibodies can be differentiated into antibodies against nuclear antigens (ANAs) and antibodies against cytoplasmic antigens (ANCAs). Although both of these antibodies are detectable in numerous autoimmune diseases, elevated ANAs are typical for connective tissue diseases and elevated ANCAs for vasculitis. Diagnosis of individual conditions can be further supported by detecting disease-specific ANAs or ANCAs, such as anti-dsDNA in systemic lupus erythematosus or c-ANCA in granulomatosis with polyangiitis.

Brief description
- ANAs comprise numerous antibodies against specific nuclear antigens.
- In addition, ANAs include autoantibodies against DNA and histones.
Assessment
- Elevated ANA levels are observed in various autoimmune diseases, especially in the diseases listed below.
- An increase is typically observed in connective tissue diseases, but may also be found in, e.g., rheumatoid arthritis (RA), autoimmune hepatitis, and vasculitides.
- In general, elevated ANA levels are considered nonspecific; exact diagnosis requires determination of individual antibodies.

Overview of ANAs
Connective tissue diseases	Antigen-specific ANAs	Other autoantibodies
Systemic lupus erythematosus (SLE)	Anti-dsDNA (in ∼ 70% of cases) Anti-Sm (Smith) Anti-histone (in drug-induced lupus erythematosus) Anti-Ro/SSA Anti-La/SSB Anti-U1 RNP (ribonucleoprotein)	Antiphospholipid antibodies (anti-cardiolipin most common type) Anti-C1q antibodies (correlates with disease activity)
Systemic sclerosis (scleroderma)	Anti-Scl-70 (anti-topoisomerase antibody I: seen in 30–70% of cases	Anticentromere Anti-RNA polymerase III
Sjögren syndrome	Anti-Ro/SSA Anti-La/SSB 60–80% of patients positive for one or both antibodies	Rheumatoid factor (RF); present in > 50% of patients Anti-CCP Salivary gland antibodies
Polymyositis and dermatomyositis	Anti-Jo1 Anti-Mi2	RF
Mixed connective tissue disease	Anti-U1-RNP	RF

References:^[1]^[2]

Description: ANCAs comprise antibodies against specific cytoplasmic antigens
Assessment
- An increase is observed in various autoimmune diseases, especially vasculitides
- Atypical fluorescence patterns of p-ANCA (perinuclear ANCA) also play an important role in the diagnosis of primary sclerosing cholangitis (PSC).

Specific ANCA	Diseases
c-ANCA (Proteinase-3 antibody)	Granulomatosis with polyangiitis: ∼ 90% of patients are ANCA positive (mostly c-ANCA). Rarely in microscopic polyangiitis, Eosinophilic granulomatosis with polyangiitis, infective endocarditis ^[3]
p-ANCA (Myeloperoxidase antibody)	Microscopic polyangiitis: ∼ 70% of patients are ANCA positive (mostly p-ANCA). Eosinophilic granulomatosis with polyangiitis: ∼ 50% of patients are ANCA positive (both c-ANCA and p-ANCA). Rarely: polyarteritis nodosa, granulomatosis with polyangiitis
atypical p-ANCA	PSC Ulcerative colitis Rarely: primary biliary cholangitis, Crohn's disease

Cytoplasmic pattern of antineutrophil cytoplasmic antibodies (c-ANCA) Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA)

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