Many Lyme disease sufferers develop arthritis weeks or months after the tick bite that transmits the disease-causing bacterium. Usually, the condition disappears following antibiotic treatments. But in roughly 10% of the patients, it mysteriously persists after the infection has vanished. Now researchers report in tomorrow's issue of Science that some people develop the persistent condition because the infection may trigger immune cells to attack both the spirochete protein and a protein found on human cells.
Patients who get persistent Lyme-related arthritis very often have immune cells that carry a particular variant molecule called DRB1*0401. Curiously, that same variant is associated with rheumatoid arthritis, an autoimmune disease. Perhaps, researchers reasoned, this variant molecule might mistake a component of human joint tissue for a protein coating the Lyme disease organism, the spirochete Borrelia burgdorferi. And indeed, in 1994, Allen Steere of the New England Medical Center in Boston and his colleagues found an antigen on the pathogen that DRB1*0401 might recognize. This OspA (for outer surface protein A) was frequently spotted by immune cells from treatment-resistant patients but recognized only uncommonly by cells from those whose arthritis responded to treatment.
Steere's group then joined forces with immunogeneticist Brigitte Huber of Tufts University School of Medicine in Boston and other colleagues to look for human proteins that might resemble OspA. When the scientists searched a database, they found one human protein that contains a similar nine-amino-acid sequence--a protein called hLFA-1, found on blood and other cells. When the researchers studied T cells from 11 patients with treatment-resistant Lyme arthritis, they found that nine of them carried T cells that respond strongly to the key sections of both OspA and hLFA-1.
The discovery could have implications for efforts to develop vaccines against Lyme disease, of which there are about 16,000 new cases every year. Just last week, two large-scale clinical trials of Lyme disease vaccines were reported to be very effective (ScienceNOW, 22 July), but both are made from the very same spirochete protein now linked to autoimmune arthritis. In theory, the protein might provoke autoimmunity in some people who receive the vaccines. Says Steere, "This is an issue of concern."