Lupus is a “mysterious” rheumatic autoimmune disease—the immune system attacks the body’s own healthy tissues, causing damage to the skin, joints, kidneys and many other organs. Such damage is mostly the result of excessive inflammation and production of antibodies, called auto-antibodies, against the body’s own tissues. Lupus is sometimes called the “great imitator,” because people often confuse the disease with other health problems—its wide range of symptoms are indeed common to many other disorders.
While some people with lupus suffer only minor inconvenience, others suffer significant lifelong disability. The signs of lupus vary depending on which body systems are affected by the disease. Fatigue and fever, joint pain, stiffness and swelling, are some of the most common symptoms. No two cases of lupus are exactly alike: signs and symptoms may come on suddenly or develop slowly, may be mild or severe, and may be temporary or permanent. Most people with lupus have mild disease characterized by episodes—called flares—when signs and symptoms get worse for a while, then improve or even disappear completely for a time.
Lupus affects people of African, Asian, or Native American descent two to three times as often as it affects whites. Nine out of 10 people with lupus are women. The disease usually strikes between age 15 and 44, although it can occur in older individuals. No single factor is known to cause lupus—rather, a combination of genetic, hormonal, environmental, and immune system factors appears to be behind it.
Now, results from a new study reveal the potential molecular mechanisms at the basis of the excessive inflammation and auto-antibody production involved in the development of lupus. The study (A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus) was carried out using human blood samples to isolate, compare and characterize different types of B cells present in healthy individuals and lupus patients. The investigators found that regulatory B cells, which in healthy individuals suppress immune responses and prevent inflammation, are not present in patients with lupus as a result of miscommunication between different cell types—B cells that produce antibodies, plasmacytoid dendritic cells that produce the cytokine interferon-alpha which functions to stimulate B cells, and regulatory B cells that suppress excessive immune responses.
Claudia Mauri, senior author of the study, said in a press release: “Our study shows for the first time that the overproduction of IFN-alpha by hyperactivated plasmacytoid dendritic cells in lupus patients is the consequence of the lack of suppressive regulatory B cells. The uncontrolled production of IFN-alpha causes an increase of antibody-producing B cells and suppresses the division and appearance of regulatory B cells.”
In their paper, the authors conclude that modulating the interactions between plasmacytoid dendritic cells and regulatory B cells could potentially create new opportunities for the development of immune-based therapies to treat patients with lupus.