Antibodies against antibodies
A team of researchers from Charité – Universitätsmedizin Berlin and Leibniz University cured two patients with systemic lupus erythematosus (SLE) using daratumumab, a monoclonal antibody that targets plasma cells. The researchers were able to modulate the impaired immunological memory processes found in these patients. The treatment gave a stable clinical response and led to a decrease in systemic inflammation.
The body's immunological memory allows the immune system to respond more quickly and effectively to pathogens it has encountered previously. This immune response is mediated by both memory T-lymphocytes and antibodies that are produced by plasma cells. Mature plasma memory cells are located in special niches of the bone marrow and are capable of producing a large number of antibodies for decades or even a lifetime. In autoimmune diseases, the immune system mistakes its own organs for foreign tissue and considers it dangerous. In a process facilitated by immunological memory, the immune system produces a response using autoantibodies. SLE is a typical autoimmune disease in which antibodies are produced against the components of the cell nuclei of the body. The autoimmune response leads to inflammation, which can affect the skin, joints or internal organs (kidneys, heart), the central nervous system. Traditional treatment is based on long-term suppression of the immune response.
A group of German researchers led by Professor Andreas Radbruch and Dr. Tobias Alexander studied the efficacy and tolerability of a specific treatment aimed at suppressing memory plasma cells in two patients with SLE who did not respond to conventional therapies. The fact is that in a certain part of patients, the disease cannot be controlled using currently available treatment methods, so there is a need for new targeted approaches.
The researchers focused their efforts on the monoclonal anti-CD38 antibody (daratumumab), which has been successfully used for many years to treat patients with multiple myeloma, a malignant tumor of plasma cells. The role of plasma cells in autoimmune diseases was the main focus of the research group.
The CD38 surface protein is considered a classic marker of plasma cells. However, preliminary studies have shown that in patients with SLE, elevated levels of this marker are also found in other active immune cells, such as memory T-lymphocytes, as well as in blood and urine. This makes CD38 an ideal target for treatment aimed at eliminating pathologically altered immune cells.
Two patients with life-threatening SLE, whose symptoms included inflammation of the heart, kidneys and anemia caused by autoantibodies, received new treatment as part of the study. Weekly administration of daratumumab for four weeks led to a rapid and significant improvement in symptoms, which did not worsen for several months after therapy. Patients also had a significant decrease in the level of autoantibodies in the blood serum. Using modern immunological methods, including sequencing of individual cells, the researchers were also able to show that daratumumab has a positive effect on active T-lymphocytes, which are believed to play an important role in the development of the disease. No side effects have been reported. Although testing showed a decrease in the amount of protective antibodies in the blood, this was not associated with increased susceptibility to infections.
The good results observed in the treatment of SLE suggest that the same success will be achieved in the treatment of other autoimmune diseases.
The authors' next step will be to test the safety and efficacy of daratumumab in a larger group of patients with SLE. To do this, the researchers plan to conduct a pilot clinical trial.
Article by L.Ostendorf et al. Targeting CD38 with Daratumumab in refractory systemic Lupus Erythematosus is published in the New England Journal of Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Charité – Universitätsmedizin Berlin: Targeting the treatment of autoimmune diseases.