Systemic Lupus Erythematosus

1. Systemic Lupus Erythematosus

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:
–
–
–
–
–
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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 3040% 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:
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–
–
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T-cells
B-cells
Complement System
Signal Transduction
• Can be lethal or not
• Unique to each individual