With today’s sophisticated analytical laboratories procedures, clinical labs can detect very small amounts of DNA present in the blood circulation and in various body tissues. DNA tests are used in medicine to help diagnose diseases such as hemachromatosis or clotting disorders. These diseases are caused by and diagnosed with tests that detect these genetic mutations. Recent research suggests that tests for DNA can also help researchers identify the disease process in various autoimmune diseases, including most connective tissue diseases, primarily rheumatoid arthritis.
According to traditional theory, human DNA is found in the nucleus or in the mitochondria of cells. In the early DNA tests, commonly used today, DNA is extracted from the body’s tissues and cells, amplified, and studied to determine specific genetic markers and mutations present on specific chromosomes. However, new findings show that free DNA (not attached to any of the body’s cells) may be attached to antibodies, primarily autoantibodies, as a DNA-antibody complex. These complexes have been found in the blood circulation of people with several different autoimmune disorders.
What Does This Mean
Researchers interpret the presence of free DNA as evidence of increased rates of cell death or cell turnover. Evidence from animal experiments and from tests performed on in vitro blood samples (outside of the body) suggest that this free DNA may play a role in the pathogenesis or process of disease development in rheumatoid arthritis.
Immune System Changes in Rheumatoid Arthritis
The pannus, a tissue composed of cells derived from synovial fibroblasts (cells that make up the joint cavity or synovium), macrophages and lymphocytes is involved in the destruction of joint cartilage and adjacent bone. Cytokines, primarily tumor necrosis factor (TNF-alpha) and interleukin-1, mediate the formation of this tissue pannus and thereby influence disease flares and remissions. The remarkable improvement seen in patients using drugs that block TNF-alpha demonstrates how potent this cytokine is.
What Causes these Changes
Researchers are interpreting the presence of free DNA to show how autoimmune disorders start with the production of autoantibodies. The complex relationships that occur between targeted antigens and their counterpart autoantibodies leads to cell and tissue destruction. In the case of both rheumatoid arthritis and ankylosing spondylitis the process, supported by the evidence of high concentrations of free DNA, leads to synovitis and joint destruction.
Resources:
Xiao-Yan Zhyone, Ines von Muhlenen, Ying Li, et. al, Increased concentrations of antibody-bound circulatory cell-free DNA in rheumatoid arthritis, Clinical Chemistry, 2007, 53:9, 1609-1614.
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