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 antibodycoated nucleus of another neutrophil. LE cells may appear in rosettes where there are several neutrophils vying for an individual complement covered protein.

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

Gambaran Klinis SLE

Limphadenopati 12-50% SSP 20% Hepotomepali/ Splenomegali 20% Sal cerna 18% Paru 38% Hematologi 50% Jantung 48% Vaskulitis Kelelahan 90% Panas 80-82% BB turun 60% Artritis/Artralgia 90% Kulit 50-58% Ginjal 50%

SLE

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.

Renal Failure because of Glomerulonephritis is the leading cause of death among lupus patients.

Normal

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
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