Lupus Exacerbations Surprise in Autoantibody Response

Researchers from Emory University School of Medicine have identified and defined a set of autoantibody-producing cells responsible for the autoimmunity profiles observed in lupus erythematosus patients. The research paper, entitled “Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus” was published in Nature Immunology.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, characterized by intermittent exacerbations (flares) of symptoms, such as inflammation and swelling of joints, fatigue, skin rashes and arthritis. As in other autoimmune diseases, the immune system of lupus’ patients attacks healthy tissue by producing antibodies against self-proteins. This loss of self-tolerance is not fully understood and has led researchers Iñaki Sanz, MD, and Chris Tipton, PhD, to investigate the origins and diversity of cells producing these harmful auto-antibodies. While the researchers did not directly investigate the effects of drugs used to treat lupus, their observations could help in drug development, as they specifically define the subsets of antibody-producing cells that are most harmful to patients.

The immune system can produce several types of antibodies, either specific for infectious viruses (good) or against human proteins as in lupus (harmful). Each cell that produces antibodies carries DNA rearrangements that dictate the makeup of its antibody product. Using next-generation sequencing technology, scientists used DNA to identify and track that cell, similar to identifying an item by its bar code. Researchers compared blood samples from eight lupus patients and eight healthy individuals recently vaccinated against influenza or tetanus to observe and compare the immune system’s responses and antibody production.

The team observed that when the immune system was responding to something it has seen before, like a booster vaccine, the “bar codes” of the antibody-producing cells looked quite identical to each other, and only a small set of antibody-producing cells multiplied and expanded. In contrast, in lupus patients many different cells were producing antibodies.

“We expected to see an expansion of the cells that produce autoantibodies, but instead we saw a very broad expansion of cells with all types of specificities,” Dr. Tipton stated in a press release. This unspecific response leads to the uncontrolled autoimmunity response observed in lupus patients, unlike differs from other autoimmune diseases, such as multiple sclerosis, where autoantibodies are directed to specific proteins of the nervous system. In their paper, the researchers also identified that some of the autoantibody-producing cells derive from a pool of “activated naïve” B cells.

The researchers said these results “should facilitate the design of future therapies,” as they identify subsets of antibody-producing cells that most trouble lupus patients during disease flares.