Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by malfunctions of T-cells, B-cells, and the complement system. It causes the immune system to produce antibodies that attack the body's own tissues and organs. SLE can affect many different body systems, including the skin, joints, kidneys, heart, lungs, blood vessels, and brain. Common symptoms include fatigue, rashes, arthritis, and kidney problems. There is no cure for lupus, but treatment options can help control symptoms. The causes of lupus are unknown, but genetic and environmental factors likely play a role in its development.

1. Systemic Lupus
Erythematosus
Steve Beesley

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

3. 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.

4. 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

5. 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

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

7. 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

8. Other Manifestations
• Cardiac
• Central Nervous System
• Hematological

9. 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

10. 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

11. 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

12. T-cell Signal Transduction

13. 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

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

15. 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

16. 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

17. FANA
• ELISA Test
– Generally test for:
• ds-DNA antibodies
• Antihistone
antibodies
– Binds to DNA,
major
constituent of
chromatin
• Deoxyribonucleopr
otein (DNP)

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

19. 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