Autoimmune Diseases

Autoimmunity Basics - Tolerance Lost & Found (Not!)

• Autoimmunity: Immune system mistakenly attacks self-tissues due to failure of self-tolerance.
• Self-Tolerance: Body's unresponsiveness to its own antigens.
  • Central: Deletion of self-reactive T cells (thymus) & B cells (bone marrow).
  • Peripheral: Anergy, suppression by Tregs, or apoptosis of escaped self-reactive cells.
• Breakdown of Tolerance:
  • Genetic: HLA associations (e.g., HLA-B27: Ankylosing Spondylitis; HLA-DR3/DR4: T1DM, RA).
  • Environmental: Infections (molecular mimicry, bystander activation), drugs, tissue injury.
  • Hormonal: Estrogen often ↑ autoimmunity risk.

⭐ Molecular mimicry: Microbial antigens resemble self-antigens, triggering autoimmunity (e.g., Rheumatic Fever post-Streptococcal infection).

SLE Spotlight - Wolf's Masquerade

Chronic, multi-system autoimmune disease. Pathogenesis: Type III Hypersensitivity Reaction (immune complex deposition).

• Key Autoantibodies:
  • ANA: Sensitive (screening).
  • Anti-dsDNA: Highly specific; correlates with nephritis activity.
  • Anti-Sm: Most specific diagnostic marker.
• Clinical Criteria: 📌 SOAP BRAIN MD (mnemonic for ACR/EULAR criteria)
  • Serositis (pleuritis or pericarditis)
  • Oral ulcers (painless)
  • Arthritis (non-erosive, ≥2 joints)
  • Photosensitivity (rash after UV exposure)
  • Blood disorders (hemolytic anemia, leukopenia, thrombocytopenia)
  • Renal (proteinuria >0.5 g/day or cellular casts)
  • ANA positive
  • Immunologic (anti-dsDNA, anti-Sm, antiphospholipid Abs)
  • Neurologic (seizures, psychosis)
  • Malar rash (butterfly rash)
  • Discoid rash (scarring plaques)
• Cardiac: Libman-Sacks endocarditis (sterile, verrucous vegetations on valves).

⭐ Anti-dsDNA and Anti-Sm antibodies are highly specific for SLE.

RA & Sjogren's - Joint & Dry Misery

• Rheumatoid Arthritis (RA):
  • Pathogenesis: Type IV HSR; CD4+ T cells, cytokines (TNF-α, IL-1); pannus formation (inflamed synovial tissue).
  • Clinical Features: Symmetrical polyarthritis (small joints: MCP, PIP); morning stiffness >1hr; deformities (swan neck, boutonniere, ulnar deviation). Extra-articular: nodules, vasculitis.
  • Antibodies: Rheumatoid Factor (RF), Anti-CCP (highly specific).
• Sjogren's Syndrome (SS):
  • Pathogenesis: Autoimmune lymphocytic infiltration of exocrine glands (lacrimal, salivary).
  • Clinical Features: Keratoconjunctivitis sicca (dry eyes), xerostomia (dry mouth). Risk of B-cell lymphoma.
  • Antibodies: Anti-Ro/SSA, Anti-La/SSB. (📌 RoLanda has Sjogren's with SS-A and SS-B).

⭐ Anti-CCP antibodies are more specific for Rheumatoid Arthritis than Rheumatoid Factor.

Organ-Specific Autoimmunity - Organ Under Siege

• Hashimoto's Thyroiditis: Autoimmune destruction (Type II & IV HSR) → hypothyroidism. Antibodies: Anti-TPO, Anti-Tg. Histo: Lymphocytic infiltrate, Hurthle cells.
• Graves' Disease: Type II HSR, TSH-Receptor stimulating antibodies (TSI) → hyperthyroidism, exophthalmos. Antibodies: Anti-TSHR.
• Myasthenia Gravis: Type II HSR, Anti-AChR antibodies at NMJ → fluctuating muscle weakness (ptosis, diplopia), worse with exertion.

  ⭐ Myasthenia Gravis is frequently associated with thymic hyperplasia (approx. 65%) or thymoma (approx. 10-15%).

High‑Yield Points - ⚡ Biggest Takeaways

• Molecular mimicry & epitope spreading are key pathogenetic mechanisms in autoimmunity.
• Strong HLA associations are common (e.g., HLA-B27 with Ankylosing Spondylitis).
• SLE: ANA is sensitive; anti-dsDNA & anti-Sm are highly specific markers.
• Rheumatoid Arthritis: Symmetric small joint arthritis; Rheumatoid Factor (RF) & anti-CCP positive.
• Sjögren's Syndrome: Sicca symptoms (dry eyes/mouth); Anti-Ro/SSA & Anti-La/SSB characteristic.
• Systemic Sclerosis: Fibrosis is hallmark; Anti-Scl-70 (diffuse), Anti-centromere (CREST).
• Autoimmunity often involves Type II, III, & IV hypersensitivity reactions.