Systemic Lupus Erythematosus - Causes

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Cytokines. Most immune cells secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for maintaining the balance of the body during immune responses, including:

• Infections
• Injuries
• Tissue repair
• Blood clotting
• Dlearing of debris from inflamed blood vessels
• Other aspects of healing.

If overproduced, however, they can cause serious damage, including dangerous levels of inflammation and cellular injury. Specific cytokines called interferons and interleukins play a critical role in SLE by regulating the secretion of autoantibodies by B cells. Researchers are currently interested in interferon alpha. Some evidence suggests high levels of this cytokine may underlie the autoimmune response in SLE.

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Complement. Another immune factor of high interest in SLE is the complement system. This is comprised of more than 30 proteins and is important for defending and regulating the immune response. Inherited deficiencies in certain complement components (C1q, C1r, C1s, C4, and C2) have long been associated with SLE. Deficiencies may contribute to SLE in the following manner:

• The complement system may protect against autoimmune disease by normalizing apoptosis, the natural process by which cells self-destruct. This self-destruction process is an important part of the normal way in which the body cleans out damaged or no longer useful cells. In healthy people, autoantibodies may also play a role in regulating apoptosis so that dangerous antigens are not left in the bloodstream long enough to trigger a more global (dysregulated) immune response.
• Complement components are also necessary for clearing molecular rubble called immune complexes. These are the end product of the battle between autoantibodies and antigens. In the absence of complement, this debris accumulates and is deposited in the kidneys, blood vessels, joints, and other sites where it can cause the immune system to produce inflammation and tissue damage.

Genetic Defects

Researchers estimated that 20 - 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 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 may predispose 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.