Systemic Lupus

Erythematosus
Alni Dwi Cahyani
 Definisi
SLE adalah penyakit peradangan kronik
multisistem yg dihubungkan dengan
ketidaknormalan sistem imun. SLE
berpengaruh pd kulit, persendian &
membran serosa (pleura, perikardium),
jantung, ginjal, sistem hematologi &
neurologi (Lewis et al, 2004)
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.
 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
 Gambaran Klinis SLE
Limphadenopati Kelelahan
SSP 12-50% 90%
20% Panas
Hepotomepali/ 80-82%
Splenomegali BB turun
20% 60%

Sal cerna
SLE Artritis/Artralgia
90%
18%
Kulit
Paru 50-58%
38% Ginjal
Hematologi 50%
Jantung Vaskulitis
50%
48%
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

• Malar or Butterfly Rash

• Discoid Rash –
Stimulated by UV light

• Skin manifestations
only appear in 30-40%
of lupus patients.
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.
Normal
• Renal Failure because of
Glomerulonephritis is the
leading cause of death
among lupus patients.

Glomerulonephritis
Other Manifestations
• Cardiac
• Central Nervous System
• Hematological
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
• 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
• Fc region switch
– ζ  εγ
– Leads to malfunction in signaling and
decreased IL-2 production
• Increased levels of Ca2+
– Leads to spontaneous apoptosis
T-cell Signal Transduction
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 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 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
• 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
FANA
• ELISA Test
– Generally test for:
• ds-DNA antibodies
• Antihistone
antibodies
– Binds to DNA,
major
constituent of
chromatin
• Deoxyribonucleopr
otein (DNP)
Ouchterlony Test
• Used to determine
immunological
specificity
• Rules out a false
positive
• Shows the serum
does or does not
have antinuclear
antibodies
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