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What causes lupus?


There is no known single cause of lupus. However, there are a number of well studied factors which undoubtedly contribute to the disease.


In simple terms, lupus is thought to be a condition with an inherited tendency for the immune system to go into overdrive. Some of the factors which are known to light the touch paper' include ultraviolet (UV) light, stress and hormone changes. A number of infectious as well as environmental factors are also suspected.


Key points

  • Hereditary tendency

  • Overactive immune system

  • Influenced by hormones

  • Possible environmental triggers


Genetics

Family and twin studies have shown convincingly that lupus has a hereditary tendency.


Lupus patients frequently have family histories of lupus, or of other autoimmune diseases. There are also numerous reports of large families with multiple cases of lupus.

Studies of twins with lupus are also interesting - the chance of an identical twin of a lupus patient developing the disease is 60%. For the geneticist, this figure suggests two things: firstly, that lupus has a definite genetic tendency and secondly, that this genetic predisposition is not the only factor in the disease (the twin statistic would be far higher in that case). Thus lupus is a disease of 'soil and seed' - genetics and environment.


The immune system in lupus

'A city where normal controls fail, law and order is poor, and the household rubbish lies on the street.' This, so the theory goes, is what happens in active lupus - the normal immune 'surveillance' breaks down, and the normal mechanism for removing cell 'waste' fails.


The normal, healthy immune system protects against foreign invaders such as viruses, bacteria or toxins by mounting what is called an 'immune response. This response comes in two main forms - immune cells and protein antibodies. There are two main types of immune cells:

  • T cells - the controlling or suppressor cells; and

  • B cells - the worker cells which produce the antibodies.

In lupus there is an impaired suppressor response (loss of police control) and the worker B cells go into overdrive and produce excess antibodies. These antibodies can, in turn, cause damage to vital body parts such as the blood vessels and the blood cells.


More recently, a second and important defect has been found. The normal immune system not only neutralises invaders but plays an important part in 'rubbish clearance' - the removal of dead or damaged cells (the scientific term is apoptosis). Failure of this important role leads to a potentially damaging build up of unwanted material.

Much has been learnt about the ways in which the various cells in the immune system communicate with each other, and this knowledge has paved the way for a whole new generation of designer drugs.


In future, rather than giving immunosuppressives which are, sadly, capable of poisoning the good cells as well as the bad cells, drugs which specifically pinpoint certain cells will be the order of the day.


One such targeted treatment already showing great promise is rituximab (Mabthera®). This drug targets a specific marker (CD 20) on B cells and has a powerful effect on these antibody-producing cells.


Hormones

Why, in lupus clinics throughout the world, is the female:male ratio always 9:1? Why women?


Why does lupus flare pre-menstrually and, conversely, often stabilise at the time of the menopause?


It is clinically abundantly clear that sex hormones must play a part in the disease, and research has supported these observations. It is also known that these hormones (notably the female sex hormone oestrogen) can have a major impact on the working of the immune system. One obvious reason for this is pregnancy: the woman carries a fetus which by definition is half foreign; the pregnant woman's immune system must be able to deal with this to avoid rejection of the fetus.


Researchers have shown that ostrogen can, in lupus, heighten the immune response, while the male hormone testosterone has the opposite effect. Sadly, although many studies have been carried out, it has not been possible to convert this knowledge into clinical practice as yet.

The environment

Our lack of knowledge of the precise triggers in lupus has not stopped us building up a list of suspected environmental factors. These include viruses, sunlight, toxins and drugs, to name but a few, and will be discussed in the next blog.

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