Autoantibodies are immunoglobulins (mainly IgG, IgM, or IgA) produced by B cells that mistakenly recognize self-antigens as foreign. Their presence usually reflects a breakdown in immune tolerance, a process where the immune system fails to ignore “self” molecules.

While healthy individuals can occasionally produce natural autoantibodies (often low-affinity and transient), pathogenic autoantibodies tend to be:

• High-affinity
• Persistent
• Isotype-switched (often IgG)
• Capable of forming immune complexes or activating complement

Autoantibodies are valuable in clinical settings because they:

• Can precede disease onset by months or years
• Often have disease specificity
• Allow early and differential diagnosis
• Assist in disease subclassification
• Sometimes correlate with disease severity or progression

Moreover, autoantibodies are stable in serum, making them ideal candidates for blood-based diagnostics using ELISA, indirect immunofluorescence, and multiplex immunoassays , see more.

1. Antinuclear Antibodies (ANA)

Definition: ANA are a broad group of autoantibodies that bind to nuclear components, such as DNA, histones, ribonucleoproteins, and nucleolar structures.

Detection: Typically identified using indirect immunofluorescence (IIF) on HEp-2 cells, which reveals different staining patterns (homogeneous, speckled, nucleolar, etc.).

Diseases Associated:

• Systemic lupus erythematosus (SLE) – Present in >95% of cases.
• Sjögren’s syndrome
• Systemic sclerosis
• Mixed connective tissue disease
• Autoimmune hepatitis

Limitations:

• ANA is sensitive but not specific.
• Low-titer ANA may appear in healthy individuals, especially older adults.

2. Anti-dsDNA Antibodies

Highly specific for: Systemic lupus erythematosus (SLE)

Clinical Relevance:

• Titer correlates with disease activity
• Associated with lupus nephritis
• Quantified by ELISA or Crithidia luciliae immunofluorescence

3. Anti-Smith (Sm) Antibodies

Specific for SLE, although only found in 10–30% of patients.

Sm antibodies are directed against snRNP (small nuclear ribonucleoproteins) and are often included in multiplex autoantibody panels.

4. Anti-Ro/SSA and Anti-La/SSB

• Present in Sjögren’s syndrome and neonatal lupus
• Associated with photosensitivity and congenital heart block in newborns
• Can be positive even when ANA is negative, especially in subacute cutaneous lupus

5. Anti-Scl-70 (Topoisomerase I) and Anti-Centromere Antibodies

These are markers for systemic sclerosis (scleroderma):

• Anti-Scl-70 → diffuse cutaneous subtype, associated with interstitial lung disease
• Anti-centromere → limited cutaneous subtype, linked to CREST syndrome

6. Anti-Citrullinated Peptide Antibodies (ACPA)

Definition: ACPAs target peptides containing citrulline, a post-translationally modified form of arginine generated by peptidylarginine deiminases (PADs).

Clinical Relevance:

• Highly specific for rheumatoid arthritis (RA) (>95%)
• Present years before symptom onset
• Predictive of erosive joint disease
• Often measured using anti-CCP ELISA (cyclic citrullinated peptide)

Why Are They Important?

Unlike rheumatoid factor (RF), which lacks specificity, ACPA are highly specific and help distinguish RA from other inflammatory arthritides.

7. Anti-Phospholipid Antibodies

Including anti-β2 glycoprotein I, anticardiolipin, and lupus anticoagulant:

• Involved in antiphospholipid syndrome (APS)
• Linked to thrombosis, pregnancy loss, and livedo reticularis

Often found in both primary APS and secondary APS (especially in lupus patients).