By Amy Maxmen of Nature magazine

Some patients with Lyme disease still show symptoms long after their treatment has finished. Now proteins have been discovered that set these people apart from those who are easily cured.

People who experience the symptoms of Lyme disease, which include fatigue, soreness and memory or concentration loss, after treatment for the disorder are sometimes diagnosed as having chronic Lyme disease or post-Lyme disease syndrome. But these diagnoses are difficult to make, because the individuals no longer seem to harbour the bacteria that cause Lyme disease. And the symptoms could instead be indicative of chronic fatigue syndrome or depression.

Now Armin Alaedini at Weill Cornell Medical College in New York and his colleagues have found that patients diagnosed with post-Lyme disease syndrome have antibodies that suggest they carried the infection for an unusually long time. The finding, published in Clinical Immunology, might help the syndrome to be better understood, diagnosed and treated.

Alaedini's team looked at antibodies made in response to a protein called VlsE, which is found on the surface of Borrelia burgdorferi, the tick-borne bacterium that causes Lyme disease.

The antibodies recognize a snippet of the protein called an epitope, and recruit the immune system to attack the bacterium. The researchers found that post-Lyme sufferers have a greater variety of antibodies to this epitope than patients whose infection cleared up quickly.

This finding suggests that patients with chronic symptoms have experienced a prolonged infection, caused by microbes that have evaded the immune system by varying the epitopes they carry. As a result of these variations, the body makes new antibodies targeting the modified protein. The longer the microbe manages to keep changing, the more diverse its host's antibodies become.

Some post-Lyme sufferers had varied antibodies against VlsE epitopes despite being diagnosed and treated early, says Alaedini. "That could mean they naturally have a different antibody response to the infection than most people; it could mean they weren't treated properly; or it's possible they were reinfected and the second infection was never treated," he says.

Inflammatory role

"This is the first study I've seen that shows some immunologic difference between someone who resolves their Lyme and someone who develops post-Lyme disease syndrome," says Linda Bockenstedt, a rheumatologist and immunologist at Yale School of Medicine in New Haven, Connecticut.

The presence of varied antibodies hints that the chronic symptoms could be caused by an ongoing inflammatory response caused by antibodies mistakenly reacting to the body's own proteins, Bockenstedt suggests.

"The big question to me is whether this can lead to an autoimmune phenomenon," says Bockenstedt. "But if that were the case, I'd expect the disease to worsen without immune-modulating treatment, and it doesn't."

If these antibodies are unique to people with chronic Lyme disease, it could lead to a test and treatments for the disorder, Alaedini says. It could also guide treatment of the disease itself. "If patients with an acute infection develop antibodies to these epitopes, perhaps they require a more aggressive course of therapy," he adds.Alaedini suggests that higher levels of antibodies could increase the body's levels of cytokines, immune-system proteins that can trigger the symptoms experienced by patients with post-Lyme disease syndrome. "Various cytokine profiles have been associated with fatigue, anxiety and depression," he explains.

But a predictive marker won't be useful without new therapies for the persistent symptoms, says Henry Feder Jr, a physician specializing in infectious diseases at the University of Connecticut Health Center in Farmington. If an immune response problem leads to the syndrome, antibiotics won't help. "I guarantee you that if you tell a patient they won't feel better after antibiotics, they won't," Feder says. "We need to know what's going on."

This article is reproduced with permission from the magazine Nature. The article was first published on August 5, 2011.