Autoimmune Diseases

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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.

T cell tolerance mechanisms & therapeutic targets

⭐ 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.

Symptoms of Systemic Lupus Erythematosus (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.

Sjogren's Syndrome Salivary Gland Infiltration

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%). Myasthenia Gravis Neuromuscular Junction Autoimmunity

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.

Practice Questions: Autoimmune Diseases

Test your understanding with these related questions

Which of the following auto antibodies is most likely to be present in a patient with systemic lupus erythematosus?

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Flashcards: Autoimmune Diseases

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_____ amyloidosis is characterized by systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA)

TAP TO REVEAL ANSWER

_____ amyloidosis is characterized by systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA)

Secondary

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