Systemic lupus erythematosus (SLE) PATHOPHYSIOLOGY شرح بالعربي : الذئبة الحمراء باثوفسيولوجي

Systemic lupus erythematosus (SLE)PATHOPHYSIOLOGY شرح بالعربي : الذئبة الحمراء باثوفسيولوجي
• Systemic lupus erythem...
Lecture outline
-Self vs non-self.
-Definition.
-Pathogenesis
-Pathology
-Aetiology
Self vs Non-self
The immune system has the capacity to distinguish between body cells (‘self’ ) and foreign materials (‘non-self’ )
It will react to the presence of foreign materials with an immune response that eliminates the intruding material from the body
All nucleated cells of the body possess unique and distinctive surface molecules that identify it as self
These self markers are called major histocompatibility complex molecules (MHC class I ) and function as identification tags.
The immune system will not normally react to cells bearing these genetically determined markers (self-tolerance)
Any substance that is recognised as foreign and is capable of triggering an immune response is called an antigen (non-self )
Definition
Systemic lupus erythematosus (SLE) is an inflammatory, multisystem autoimmune disorder
with arthralgia and rashes as the most common clinical features,
and cerebral and renal disease as the most serious problems. 
Prevalence
Systemic lupus erythematosus (SLE) is a rare disease with a prevalence that ranges from about 0.03% (3/10000) in people of European descent to 0.2% (20/10000)
in people of African Caribbean origin.
Some 90% of affected patients are
female and the peak age at onset is between 20 and 30 years.
Importance
SLE is associated with considerable morbidity and a five fold increase in mortality compared to age- and gender-matched controls, mainly because of
an increased risk of premature cardiovascular disease.
Pathogenesis
When cells die by apoptosis, the cellular remnants appear on the cell surface as small blebs that carry self antigens.
These antigens include nuclear constituents (e.g. DNA and histones), which are normally hidden from the immune system.
In people with SLE, removal of these blebs by phagocytes is inefficient,
so they are transferred to lymphoid tissues, where they can be taken up by antigen-presenting cells, so they can be presented to T cells, which in turn stimulate B cells to produce autoantibodies directed against these antigens,
This is called Breakdown of tolerance
Breakdown of tolerance results in
-Development of autoantibodies that either form circulating complexes or deposit by binding directly to tissues.
-Activation of complement and influx of neutrophils, causing inflammation in those tissues.
-Abnormal cytokine production: increased blood levels of IL-10 and interferon-alpha.
Aetiology
Heredity
There is a higher concordance rate in monozygotic twins (up to 25%) compared with dizygotic twins (3%).
First-degree relatives have a 3% chance of developing the disease but approximately 20% have autoantibodies.
Genetics
20 genes are linked to the development of SLE.
These include some HLA genes, as well as genes involved in T- and B- lymphocyte function and genes related to autophagy
and interferon function.
Homozygous deficiencies of the complement genes C1q, C2 or C4 are very rare but convey a high risk of developing SLE.
Drugs
Drugs such as hydralazine, isoniazid, procainamide and penicillamine can induce a form of SLE .
It is usually mild, in that the kidneys and central nervous system are not affected.
Other factors
Sex hormone status
Pre-menopausal women are most
frequently affected.
Ultraviolet light.
This can trigger flares of SLE, especially in the skin.
Exposure to Epstein-Barr virus.
This has been suggested as a trigger for SLE.

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