Some Autoimmune Disorders

Autoimmune thyroiditis disease (Robbins pp 1133-1137)

Hashimoto’s thyroditis

• More common in females 10:1 – 20:1.
  
• More prevalent between ages 30-50 yrs old.
  
• It was first reported in 1912 by Hashimoto describe goitre and intense lymphocytic infiltration.
  
• Most common cause of hypothyroidism in areas with sufficient iodine levels.
• In this disease, autoantibodies against thyroglobulin and thyroxidase (target antigens) activate the complement system or CD8+ cells≫ lyse/cell death.

Grave’s disease (thyrotoxicosis)

• Causes hyperthyroidism.
  
• IgG antibodies (autoantibodies) bind to target antigen ≫ receptors for thyroid stimulating hormone , which increases adenylate cyclase activity ≫ increase thyroid hormone activity.

Thus, there are three mechanisms in which autoimmune reactions may attack the thyroid. i.e.: autoantibodies activating the complement system causing cell lysis, autoantibodies activating cytotoxic T cells causing cell death or autoantibodies causing an increase in thyroid activity.

Multiple sclerosis (Robbins pp 1326)

• MS is prevalent is most areas of the world, having an incidence of 1 in 1000 people in USA.
• It has been suggested incidence rates increase as distance increases from the equator.
  
• Genetic link clearly evident.
  
• It has been established that if you have DR2 extended haplotype of the MHC that MS susceptibility increases.
  
• MS is the most common demyelinating condition of the CNS.
  
• Clinical features: unilateral vision impairment (optic neuritis), ataxia, nystagmus, spinal cord lesions give rise to motor and sensory impairment of trunk and limbs, impairment of voluntary control of bladder & spasticity.
  
• Pathogenesis: mononuclear infiltration of CNS lesion (CD4+ & CD8+ & macrophages) ≫ induce oligodendrocyte injury (via Fas-Fas ligand system).
  
• Increased IgG found in CSF. A transmissible infectious agent has been proposed but no a well characterised virus is yet to be identified.

Systemic Lupus Erythaematosis (Robbins 217)

• This is a classic multisystem autoimmune disease (organ-non-specific) prototype.
  
• It affects young woman of child bearing age, female to male ratio 9:1.
  
• Clinical features include: butterfly rash over face, fever, malaise, pain over joints, lethargy, weight loss.
  
• Diagnosis is confirmed by detection of ANA to ds, ss, DNA & histones and Sm antigen.

Rheumatoid Athritis (Robbins 1249,)

• This is a chronic inflammatory joint disease.
  
• Clinical features: malaise, fatigue, musculoskeletal pain, weakness. RF (IgM) deposits in joint tissues causing the autoimmune reaction.
• Rheumatoid factor is mostly IgM (they are actually autoantibodies to the Fc portion of IgG antibodies).
  
• Immune complexes form in joints, complement activation ≫ inflammation (“frustrated phagocytosis”).

Category: Pathology Notes