Why the body’s immune cells cause so much damage

The reason why the body's immune cells cause so much damage and can't regulate themselves in patients with lupus has been revealed in a UCL study published in the journal Immunity, a finding which could lead to more effective ways of treating lupus. Using blood samples from 88 healthy people and 217 lupus patients, the team found that immune cells, which regulate the immune response and reduce inflammation, are instead being turned into autoantibody-producing B cells that cause inflammation. This miscommunication in lupus patients is caused by an imbalance of three types of immune cells: B cells that produce antibodies to protect the body against foreign microbes (and a main driver of autoimmune disorders); plasmacytoid dendritic cells that produce a molecular signal called interferon-alpha (IFNa) that stimulates B cells; and regulatory B cells that suppress excessive immune responses. "Our study shows for the first time that the overproduction of IFNa by hyperactivated plasmacytoid dendritic cells in lupus patients is the consequence of the lack of suppressive regulatory B cells," says senior author Professor Claudia Mauri (UCL Inflammation). "The uncontrolled production of IFNa causes an increase of antibody-producing B cells and suppresses the division and appearance of regulatory B cells." The researchers also discovered a potential reason why rituximab, a drug that has been used off-label to treat lupus by depleting the vast majority of circulating B cells, benefits some patients but not others.