Blood samples of patients with systemic lupus erythematous (SLE) contain previously unrecognized structures that may serve as markers for disease activity. Called microparticles (MPs), these structures (contain both mitochondrial proteins and immunoglobulin G (IgG). SLE primarily affects young women, leading to inflammation and tissue damage.
Published in the Journal of Autoimmunity, the findings represent another advance in a series of studies examining the nature of immune complexes in SLE and the role of MPs as a marker for SLE. One of the authors was Duke rheumatologist David S. Pisetsky, MD, PhD.
“This research was focused on the nature of immune complexes in the blood of patients with lupus, but we believe the findings may generalize to other diseases,” says Pisetsky, who is a leader in research involving the immune complexes associated with SLE. “The same phenomenon probably exits with rheumatoid arthritis (RA) in the joints as opposed to the blood.”
The study’s conclusion was based on an examination of the size of the MPs, the IgG expression, the content of nucleic acids and mitochondrial molecules, Pisetsky says. The levels of these MPs are related to several measures of active SLE, suggesting that determining the numbers of these structures in the blood could help determine whether disease is active and causing inflammation.
The commonly accepted model of immune complexes has been based on idea that the antibodies bind to antigens that are circulating in the blood. In SLE, these complexes contain DNA. Pisetsky says. “But In truth, it has always been difficult to find immune complexes in the blood pf patients with lupus even if there some was evidence that they were present. They were simply hard to find. While the presence of DNA was expected, the large size of the MPs and the presence of mitochondrial material were a total surprise.” Mitochondria play a role in energy metabolism.
Sometimes referred to as an antigen-antibody complex, an immune complex can cause illness when deposited in organs. In patients with SLE, the antibodies are deposited in the kidneys and are a cause of nephritis. A key aspect of the research, Pisetsky says, is the recognition of larger particles as clues to the identification of the immune complex. These particles can be readily measured by a technique called flow cytometry, which is available in clinical laboratories.
“The general model of the immune complex has always based of the idea that the antibody binds to antigens such as proteins or DNA which are relatively small in molecular terms,” Pisetsky says. “It has always been difficult to find evidence of the complexes in the blood of patients with lupus even though there was always evidence the complex existed there. We can now focus on relatively larger particles in future research. We can also try to determine why mitochondria have left cells and are present in the blood to form complexes.”