Myalgic encephalomyelitis, or chronic fatigue syndrome, is a perplexing disorder that may seem more like a voodoo hex than an illness. Patients might lie bedridden in dark rooms, in chronic pain, often with multiple neurological symptoms like muscle pain, sweating and dizziness.
Doctors have targeted various causes, from herpes viruses to retroviruses to depression. But a surprising new explanation suggests that the disorder is an autoimmune disease of the nervous system caused by overactive B-cells, which are normally responsible for churning out pathogen-killing antibodies.
In 2011, two Norwegian oncologists, Oystein Fluge and Olav Mella of Haukeland University Hospital in Bergen, along with colleagues, studied 30 people diagnosed with chronic fatigue immune dysfunction syndrome (CFIDS). Each received either a placebo or a highly specialized chemotherapy drug called rituximab, which rapidly and selectively depletes B-cells. After 12 months, 10 of 15 patients on the drug significantly improved; only two of 15 on the placebo improved.
This study marks just one more step in a growing body of research focusing on the role of B-cells in autoimmune disease. While they’re essential for helping the body fend off attacks, if something goes awry, B-cells can generate antibodies that attack healthy tissues.
Until recently, T-cells — cells that activate and regulate the molecules responsible for controlling inflammation and immune response — were considered the great orchestrators of immunity. They were also thought to be the main drivers of autoimmune disorders.
In turn, researchers considered B-cells to be the worker bees taking the T-cells’ orders. “T-cells were in fashion for a long time,” says retired rheumatologist and researcher Jonathan Edwards. “B-cells were just considered boring.” But Edwards was never convinced that T-cells were the alpha and omega of immunity.
As it turns out, B-cells play a major, and sometimes independent, role in immune function, dancing with T-cells in a fluid and Escher-like loop. For instance, specific anti-T-cell therapies don’t work at all for rheumatoid arthritis (RA), and Edwards doesn’t think T-cells explained how the disease persisted. He and his colleagues at University College in London worked for a decade piecing together a hypothesis on the role of B-cells in RA, and they then began to test it.
In 2004, their landmark study in the New England Journal of Medicine changed how researchers approached RA. Their randomized trial followed 161 patients treated either with a conventional immune-suppressing drug called methotrexate, or with methotrexate plus rituximab, the B-cell killer. More than 40 percent of patients given the drug combination experienced major improvement by the end of 24 weeks, and they sustained that improvement for another 24 weeks. Only 13 percent of those receiving methotrexate alone improved.
“T-cells and B-cells cooperate with each other,” says Edwards, “and we think the B-cells can sometimes make a mistake, create auto-antibodies and fool the T-cells into giving them permission to continue doing so. We deplete the B-cells, the antibodies gradually disappear, and people improve, but eventually the B-cell population rebounds and people need re-treatment.”