systemic lupus erythematosus l.
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Systemic Lupus Erythematosus. Steve Beesley. History. 1948 – Malcolm Hargraves discovers the lupus erythematosus (LE) cell. 1957 – The first anti-DNA antibody is identified. The LE cell is a neutrophil that has engulfed the antibody-coated nucleus of another neutrophil.

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

LE Cell
genetic associations
Genetic Associations
  • HLA’s are loci on genes that code for certain β chain on the MHC complex
  • HLA-DR2
  • HLA-DR3
  • HLA-DQB1 – Involved in mediating production of antibodies to ds-DNA
symptoms
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
skin manifestations
Skin Manifestations
  • Malar or Butterfly Rash
  • Discoid Rash – Stimulated by UV light
  • Skin manifestations only appear in 30-40% of lupus patients.
renal kidney manifestations
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

other manifestations
Other Manifestations
  • Cardiac
  • Central Nervous System
  • Hematological
main pathology
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
overactive b cells
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
t cell malfunctions
T-cell Malfunctions
  • Fc region switch
    • ζ εγ
    • Leads to malfunction in signaling and decreased IL-2 production
  • Increased levels of Ca2+
    • Leads to spontaneous apoptosis
activation of complement system
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
igg pathogen
IgG Pathogen
  • IgG is the most “pathogenic” because it forms intermediate sized complexes that can get to the small places and block them.
dna is the main man
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
testing
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
slide17
FANA
  • ELISA Test
    • Generally test for:
      • ds-DNA antibodies
      • Antihistone antibodies
        • Binds to DNA, major constituent of chromatin
      • Deoxyribonucleoprotein (DNP)
ouchterlony test
Ouchterlony Test
  • Used to determine immunological specificity
  • Rules out a false positive
  • Shows the serum does or does not have antinuclear antibodies
summary
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