Done by : AbdulrahmanSulaiman Al-Otaiq
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Autoimmune disease affecting multiple organ systems
Relapsing (flares) and remitting course
Protean clinical manifestations
Etiology is unknown
Female to male ratio is 9:1
Age of onset
16 to 55 years (65%)
< 16 years (20%)
> 55 years (15%)
involvement of human leucocyte antigen (HLA) class II gene polymorphisms.
presence of anti-small nuclear ribonuclear protein, anti-nuclear ribonuclear protein and anti-DNA antibodies.
Increase in estrogen lead to ↑B cell differentiation & ↓In vitro apoptosis of PBMCs &↓TNF production,
This will leads to B cell hyperactivity and the production of pathogenic autoantibodies.
Disturbances of the immune response
Environmental antigens and self antigens are taken up by antigen presenting cells (APCs).
process the antigens into peptides & present them to T cells through their surface HLA molecules.
The activated T cells in turn stimulate the B cells to produce pathogenic autoantibodies.
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) - PATHOGENESIS
Defective regulation of apoptosis
Accelerated rate of apoptosis in macrophages mediated (in part) by T cells
T-cell mediated APC apoptosis
Defective clearance of apoptotic cells
Increased cell death with nuclear antigens exposed
DS-DNA, Smith, Sjogren’s syndrome A (SSA) and B (SSB)
Deposition of autoantibody-nuclear antigen complexes
The plasma cells are producing antibodies that are specific for self proteins, namely ds-DNA
Suppressed regulatory function in T-cells
Lack of T-cells
Activation of the Complement system
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
Fc region switch
Leads to malfunction in signaling and decreased IL-2 production
Increased levels of Ca2+
Leads to spontaneous apoptosis
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 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
Burket's Oral Medicine, chapter 5