Lupus, also known as systemic lupus erythematosus (SLE), is an autoimmune disease that causes various tissues in the body to become chronically inflamed. It can affect many parts of the body, typically the skin, joints, kidneys, various types of blood cells, the brain, and the lining of the heart and lungs. A butterfly-shaped rash across the face is a characteristic sign  of the disease. Lupus can be mild or life-threatening, depending on which parts of the body are affected.

Lupus affects one in 700 Australians. Nine out of every ten people with lupus are women, with the onset of disease usually occurring between 20 and 50 years of age. People from all ethnic backgrounds can develop the disease although it tends to be more severe in African Americans and Asians than Caucasians.

The causes of lupus

The immune system normally protects the body against foreign invaders, like bacteria and viruses. However, in autoimmune diseases like lupus, for reasons which are not fully understood, immune cells are reprogrammed to attack the body’s own cells and tissues. In addition to lupus other examples of autoimmune diseases are rheumatoid arthritis , type 1 diabetes, Sogrens syndrome and multiple sclerosis. Together autoimmune diseases of various kinds affect approximately 5% of the population.

The exact cause of lupus is unknown, although it is likely that environmental factors trigger the autoimmune attack in genetically susceptible people. As a result, autoantibodies are made to DNA and various blood cells with which they combine to form ‘immune complexes’.  These complexes are then deposited in the blood vessels supplying various organs in the body leading to tissue damage and the typical clinical features of the disease like skin rash.

The symptoms of lupus

Symptoms vary greatly between individuals and can fluctuate between active periods (flares) and times of minimal or no symptoms (remission). They include:

  • Sunlight sensitive rashes on the face and body
  • Painful inflammation of one or more joints, which may cause the disease to be mistaken for rheumatoid arthritis
  • Impaired kidney function due to severe inflammation and immune cell blockage of the blood vessels
  • Mouth ulcers
  • Chest pain due to pleurisy (inflammation of the lining surrounding the lungs)
  • Blood clotting problems
  • Hair loss
  • Unexplained headaches, fits or mood swings
  • Extreme fatigue
  • Recurrent miscarriages

Options for lupus treatment

In view of the great variation in clinical presentations, it is most important to confirm the diagnosis of lupus. This is done by performing a blood test for anti-DNA antibodies which are a hallmark of the diseases, taking biopsies of skin and other tissues to ascertain the extent of the disease and checking for abnormalities in blood cells.

In the absense of a definite cause, treatment is designed to minimise sun exposure when relevant, to suppress immune complex-induced inflammation and to restore organ function in the case of more severe disease. A range of drugs are available for this purpose including non Steroidal anti-inflammatory agents, antimalarials, and cortisone combined if necessary with cytotoxic drugs when organ function is severely impaired.

Garvan's research into lupus

The immunology division at the Garvan has a major interest in working out why a small proportion of people (<10%) make the autoantibodies that cause autoimmune diseases like lupus; and others do not.  A range of experimental models is being used for this purpose with the current focus being on a particular structure in lymph glands and spleen called the ‘germinal centre’.

The white blood cells destined to make antibodies( B lymphocytes) collect there after stimulation and normally mature into cells which produce antibodies to foreign microorganisms. According to our recent work it is becoming apparent that the maturation process in germinal centres is defective in autoimmune diseases, resulting in escape of autoantibody producing  B lymphocytes and a breakdown in immune tolerance.  

Particularly exciting in the fact that we can now visualise the selective procedure in germinal centres directly under a special 2 photon microscope. Based on such information the next step will be to devise therapeutic strategies for reprogramming the germinal centre to shut down autoimmunity. 

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