Systemic Lupus Erythematosus

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Systemic Lupus Erythematosus

• Steve Beesley

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History

• 1948 Malcolm Hargraves discovers the lupus
  erythematosus (LE) cell.
• 1957 The first anti-DNA antibody is identified.
  

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LE Cell

• The LE cell is a neutrophil that has engulfed the
  antibody-coated nucleus of another neutrophil.
• LE cells may appear in rosettes where there are
  several neutrophils vying for an individual
  complement covered protein.

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Genetic Associations

• HLAs are loci on genes that code for certain ß
  chain on the MHC complex
• HLA-DR2
• HLA-DR3
• HLA-DQB1 Involved in mediating production of
  antibodies to ds-DNA

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Symptoms

• Non-specific
• Fatigue
• Weight loss
• Malaise generally feeling ill
• Fever
• Anorexia (over time)
• Arthritis
• 90 of patients experience arthritic symptoms
• Symmetrical
• Appears in hands, wrists, and knees mainly

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Skin Manifestations

• Malar or Butterfly Rash
• Discoid Rash Stimulated by UV light
• Skin manifestations only appear in 30-40 of
  lupus patients.

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Renal (Kidney) Manifestations

• 50-70 of all lupus patients experience renal
  developments.
• Most Dangerous
• Glomerulonephritis? where at least 50 of the
  glomeruli have cellular proliferation
• Glomeruli capillary beds in the kidney that
  filter the blood.
• Renal Failure because of Glomerulonephritis is
  the leading cause of death among lupus patients.

Normal
Glomerulonephritis
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Other Manifestations

• Cardiac
• Central Nervous System
• Hematological

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Main Pathology

• The plasma cells are producing antibodies that
  are specific for self proteins, namely ds-DNA
• Overactive B-cells
• Suppressed regulatory function in T-cells
• Lack of T-cells
• Activation of the Complement system

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Overactive B-cells

• Estrogen is a stimulator of B-cell activity
• Lupus is much more prevalent in females of ages
  15-45
• Height of Estrogen production
• IL-10, also a B-cell stimulator is in high
  concentration in lupus patient serum.
• High concentration linked to cell damage caused
  by inflammation

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T-cell Malfunctions

• Fc region switch
• ? ? e?
• Leads to malfunction in signaling and decreased
  IL-2 production
• Increased levels of Ca2
• Leads to spontaneous apoptosis

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T-cell Signal Transduction
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Activation of Complement System

• Complement system is activated by the binding of
  antibodies to foreign debris.
• In this case its over activation
• RBCs lack CR1 receptor
• Decreasing the affective removal of complexes

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IgG Pathogen

• IgG is the most pathogenic because it forms
  intermediate sized complexes that can get to the
  small places and block them.

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DNA is the Main man

• DNA is the main antigen for which antibodies are
  formed.
• Extracellular DNA has an affinity for basement
  membrane where it is bound by autoantibodies.
• Classical thickening of the basement membrane

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Testing

• ESR
• Urinalysis
• Complement Test
• Tests levels of C3, C4, CH50
• Low levels indicates possible presence of disease
• FANA Fluorescent antinuclear antibody
• Ouchterlony Test shows interactions

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FANA

• ELISA Test
• Generally test for
• ds-DNA antibodies
• Antihistone antibodies
• Binds to DNA, major constituent of chromatin
• Deoxyribonucleoprotein (DNP)

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Ouchterlony Test

• Used to determine immunological specificity
• Rules out a false positive
• Shows the serum does or does not have antinuclear
  antibodies

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Summary

• Lupus Autoimmunity
• Systemic and affects connective tissue
• Caused by malfunctions of
• T-cells
• B-cells
• Complement System
• Signal Transduction
• Can be lethal or not
• Unique to each individual