Systemic Lupus Erythematosus - Causes

Genetic Defects

Researchers estimated that between 20 and 100 different genetic factors may be involved in the alterations of the immune system set point that could make a person susceptible to SLE.

Research published in 2003 identified a particular set of genes, now commonly called the "interferon signature," that is activated by interferon in patients with severe lupus. This discovery may help doctors be able to identify patients at particular risk for severe disease before they develop symptoms.
A genetic risk factor for lupus in African American women was identified in 2003. This defect causes increased production of nitric oxide,which maypredispose individuals to lupus, and to severe disease in particular.
Other research has identified defects in genes that regulate apoptosis, the natural process by which cells self-destruct.
Another study identified an abnormal gene in some patients with SLE that promotes the build-up of immune complexes that can cause kidney damage. HLA (human leukocyte antigen) is a protein that presents antigens to T cells by holding them up from the surface of macrophages or other antigen-presenting cells. There are varieties of HLA molecules that are determined by the genes that are inherited. Small differences in HLA from person to person can determine which antigens are presented in triggering an immune response and how strongly the immune system will respond to these antigens. Among the types of HLA associated with lupus are HLA-DR2, -DR3, -A1, -B8, and DMA-0104.

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Triggers of the Immune Response

In genetically susceptible people, there are various external factors that can provoke an immune response. Possible SLE triggers include colds, fatigue, stress, chemicals, sunlight, and certain drugs.

Viruses. Blood tests reveal that patients with SLE are more likely to have been exposed to certain viruses than the general population. These viruses include the Epstein-Barr virus (the cause of mononucleosis), cytomegalovirus, and parvovirus-B1.

Results from a 2005 study, conducted by researchers at the National Institute of Environmental Health Sciences, suggested a strong association between Epstein-Barr virus (EBV) and increased risk of lupus, particularly for African Americans. The study of 230 patients with lupus and matched controls assessed the seroprevalence of EBV antibodies. One particular antibody, EBV-IgA, was linked to a five times greater risk of SLE in African Americans. The association was not as strong for whites, but increased with age (patients over 50 years of age had four times higher risk.)