Autoantibodies: When the Immune System Attacks Self

Autoantibodies are immunoglobulins that target the body’s own molecules (proteins, DNA, lipids, receptors). They’re the hallmark of autoimmune diseases—but also appear in healthy people (low titer, benign).

How They Arise

• Genetic susceptibility: HLA alleles (DR3, DR4, B27), PTPN22, CTLA4, AIRE.
• Environmental triggers: Infections (molecular mimicry: EBV → lupus, Strep → rheumatic fever), drugs (hydralazine → lupus), silica, smoking (RA, anti-CCP), UV (lupus).
• Loss of tolerance: Failed central (thymic) or peripheral (Treg, anergy) checkpoints.
• Epitope spreading: Initial target → broader self-reactivity.

Major Autoantibodies & Diseases

Clinical Utility

• Diagnosis: Supportive (not standalone).
• Prognosis: Anti-dsDNA → lupus nephritis; anti-CCP → erosive RA.
• Monitoring: Anti-dsDNA, ANCA titers track activity.
• Therapy guidance: Rituximab (B-cell depletion) → autoantibody drop.

Key: Autoantibody ≠ autoimmune disease. Context (symptoms, signs, other labs) decides.